Metcalf was born in Carbondale, IL and raised in nearby Edwardsville by a librarian mother and a comptroller father who oversaw budgets at Southern Illinois University. The oldest child of three, including a brother and sister, Metcalf was, by her own admission, notoriously withdrawn. In grade school, she and her friends would put on plays for fun, but it was not until she started school at Edwardsville High School that she took her first real stab at acting, landing the small part of a fiancée in a student production. Though she had found the experience of acting to be a nice departure from her own shy persona, after a couple of plays, Metcalf still assumed she would need a permanent career in something more stable.By 1973, attending Illinois State University Normal, she started into a major in German with the hopes of becoming an interpreter, but soon grew more interested in anthropology and decided to change departments. Throughout college, the theater continued to lure her back, and she decided to rethink her take on acting after appearing in the Joe Orton play, "What the Butler Saw," for which she received positive notices. While giving one of her performances, she was spotted by theater major Terry Kinney, a fellow student whom she would befriend and subsequently fall for. A big supporter, Kinney encouraged her to continue on with acting. Metcalf agreed and ultimately graduated from the university with a theater degree in 1977. By then, she and her theater department friends had already begun pooling their considerable talents into something they hoped would become extraordinary.The group's newly minted Steppenwolf Theatre Company would feature in its early ranks future Hollywood staples John Malkovich, Joan Allen, Gary Sinise, Glenne Headly and Gary Cole, among others, and spend its first three years in a Highland Park church school basement. The 88-seat location was miraculously procured by Sinise for the annual cost of a single dollar. Spending much of their time together, the eager company became closely knit, and romantic relationships began to develop among several of the members, with Metcalf dating Malkovich before finding a more substantial romantic connection with co-member Jeff Perry. In her colleagues, Metcalf knew she had found a truly gifted and passionate group, one whose conviction allowed its members to think of acting as more than just a passing interest.With Malkovich serving as one of the company's major ringleaders, Metcalf began to explore the full breadth of her acting, rehearsing and performing in her free time while spending days working as a secretary. Very notably, in Malkovich's 1981 adaptation of Lanford Wilson's "Balm in Gilead" - widely considered to be a milestone of both Chicago, and later New York, theater - Metcalf took on the role of a tragic Midwestern prostitute, and the play's final act featured her wrenching delivery of a 20-minute monologue chronicling the character's journey from her youth through her entry into prostitution. Metcalf was not shy about taking on male roles for Steppenwolf either. It was the kind of company in which, in an adaptation of Tom Stoppard's "Rosencrantz and Guildenstern Are Dead," she could casually slip into the role of Hamlet without question. As the Steppenwolf gang was gaining a reputation for its fresh brand of theater among Chicago's theater critics, it was believed within the company, that Metcalf was becoming one of its most fearless participants.In April 1981, Metcalf was in New York City to appear as a player on NBC's stalwart "Saturday Night Live" (1975-), but her affiliation with the show lasted only one episode, due to unexpected casting shakeups. She continued to act in plays back in Chicago, such as Steppenwolf's 1982 production of Sam Shepard's "True West," and she also found time to marry fellow Steppenwolf member Jeff Perry in 1983. In 1984, when the company's version of "Balm in Gilead" made its way to an off-Broadway theater, its star returned to New York right along with it. The show, and Metcalf's delivery of that famous monologue, would be remembered by New York theater critics in the years to come, but in 1984 they stamped their approval with an Obie Award and again in 1985 with a Theater World Award and the prestigious Drama Desk Award.The buzz on Metcalf's performance brought Hollywood to the bargaining table. As Metcalf and Perry were celebrating the recent birth of daughter Zoe and mourning the death of Metcalf's father, the actress herself was getting a glimpse of just how easily Tinseltown could offer a young performer a shot at a more mainstream platform. One such member of the "Balm in Gilead" audience, film director Susan Seidelman, was making a movie called "Desperately Seeking Susan" (1985) and wanted Metcalf in it. The film would mark the big screen acting debut of pop icon Madonna, but it also served as the Edwardsville native's onscreen debut as well. Metcalf played a caustic woman of unflattering style frantically looking for married bliss. Seidelman was suitably impressed with her onscreen performance and hired her again to play another love-starved woman in "Making Mr. Right" (1987), which also starred Steppenwolf alumni Malkovich and Headly.Shortly after her work with Seidelman, Metcalf starred in a succession of films, including the half-hour short "The Appointment of Dennis Jennings" (1988) and the features "Candy Mountain" (1988) "Stars and Bars" (1988) and "Miles From Home" (1988), with Metcalf playing a stripper in the latter. All but legally divorced from Perry by this time, she was ready to make a real move and plant her roots far beyond either Illinois or New York. Uprooting her daughter, she trekked out to Los Angeles, and in her first week on the West Coast, landed a crucial part on ABC's in-development sitcom "Roseanne" (1988-1997). "Cosby Show" producer Marcy Carsey, who was one of the primary producers on "Roseanne," enthusiastically talked Metcalf up to her leading lady, comedian Roseanne Barr. The show, based on Barr's stand-up act, recalled Barr's experiences as a working wife and mother, and its fictional town of Lanford, IL was very much in sync with Metcalf's Illinois upbringing and her own hard-working, low-key sensibilities. As Roseanne Conner's sister Jackie Harris, Metcalf was able to bring to the character the mixture of doubt, humor and resolve she had been allowed to develop and express on the stage as well as through her own personal experiences.Over the course of the titular sitcom's nine seasons, Jackie stumbled through a series of romantic relationships and went through a number of career changes - starting out as a factory worker and later becoming an eatery co-owner, a police officer and a truck driver. Metcalf won three consecutive Emmy Awards for her ever-evolving portrayal in 1992, 1993 and 1994. The show also brought with it a romance when Metcalf met the actor Matt Roth, who played Jackie's violent love interest, Fisher. In real life, there was none of that onscreen combustibility to be found as the two actors unexpectedly fell in love and by November 1993, had a son, Will. With Roth, Metcalf would find happiness in marriage once more and her pregnancy even became a storyline on the show, complementing the series' occasional inclusion of daughter Zoe as the younger Jackie. Following Roth's appearance on "Roseanne," the real-life couple continued to work together sporadically, acting in the big screen thriller "Blink" (1994) and the drama "Chicago Cab" (1997). Over the summers, Metcalf enjoyed taking parts in films. She had a small role in John Hughes' "Uncle Buck" (1989), prominently played Andy Garcia's lesbian police partner in the Mike Figgis-helmed thriller, "Internal Affairs" (1990), played a lawyer in the Michael Keaton thriller, "Pacific Heights" (1990) and in her most memorable big screen role, portrayed the investigator Susie Cox, who assists Kevin Costner's D.A. Jim Garrison in Oliver Stone's controversial but beloved epic, "JFK" (1991). In 1995, she took the part of Nicolas Cage's landlord in Figgis' dark drama, "Leaving Las Vegas." A year later, Metcalf got her first introduction to the world of animated voiceover work, playing the mother of young Andy, voiced by John Morris, in Pixar's mega-hit, "Toy Story" (1995). Then, having developed a professional rapport with director Garry Marshall through their work on Marshall's and Lowell Ganz' 1990 Steppenwolf play, "Wrong Turn at Lungfish," the pair re-teamed for the Greg Kinnear holiday vehicle, "Dear God" (1996). Of course, summers also meant that Metcalf would be returning to the Steppenwolf stage she called home whenever possible. During her time off from "Roseanne," she made many memorable turns in various company-produced plays, including one as a jilted wife in Alexandra Gersten's "My Thing of Love" in 1992 and another in Malkovich's 1994 adaptation of Don DeLillo's "Libra," as both the mother of Lee Harvey Oswald and a gay man co-conspiring to assassinate President Kennedy. In April of 1995, "My Thing of Love" attempted a leap to Broadway which, despite raves for Metcalf's performance, closed after a scant 12 performances.Much as she had done on the stage, Metcalf had, by 1997, gained a solid reputation in Hollywood as one of its more multi-faceted character actresses. Directors developed a consistent habit of repeat hirings, as would become evident with Metcalf's casting in Stone's "U-Turn" (1997), Figgis' "Timecode" (2000) and Garry Marshall's "Runaway Bride" (1999). The year 1997 also marked the graceful end of "Roseanne," and Metcalf's career was such that she could now pick an over-the-top role in "Scream 2" (1997), the second installment of the popular horror franchise, before making an about-face into Warren Beatty's political satire, "Bulworth" (1998). After appearing with Laurence Fishburne in HBO's "Always Outnumbered" (1998), she finally took center stage onscreen in NBC's "The Long Island Incident" (1998), as Carolyn McCarthy, the real wife of a slain train commuter who won a congressional seat after lobbying for stronger gun laws.Without a set schedule, Metcalf found herself drawn to a wide variety of projects. She received another Emmy nomination for a guest appearance on NBC's "3rd Rock From the Sun" (1996-2001), then returned to provide the voice for her "Toy Story" character in the equally well-made "Toy Story 2" (1999). She jumped back into regular series work alongside "Roseanne" producers Marcy Carsey and Tom Werner, providing a voice on its primetime NBC cartoon "God, the Devil and Bob" (2000). Although the show lasted only 13 episodes, her next comedy, ABC's "The Norm Show" (1999-2001), featuring former "SNL" Weekend Update anchor Norm MacDonald, fared better, putting three seasons under its belt. In late July 2001, Metcalf began a successful two-month run in the London production of Arthur Miller's "All My Sons," replacing the legendary Julie Walters. She then returned to her onscreen career in Los Angeles, landing a voiceover part in Disney's animated feature, "Treasure Planet" (2002). She made another attempt at fulltime series work in CBS' Nathan Lane comedy, "Charlie Lawrence" (2003), but the series left the air almost as quickly as it appeared.In the early part of the new millennium, Metcalf segued into guest spots and small recurring roles in high profile series such as Fox's "Malcolm in the Middle" (2000-06), NBC's "Frasier" (1993-2004) and CBS' "Without a Trace" (2002-09). At age 50, Metcalf had a second child with Roth, daughter Mae, in July 2005 via a surrogate and had vacated Los Angeles for life on a quiet Idaho ranch. She took a role in the blue-collar indie film drama, "Steel City" (2006) and appeared as the mother of her "Norm Show" co-star Artie Lange in "Artie Lange's Beer League" (2006). An appearance on "Monk" (USA Network, 2002-09) in January 2006 even garnered her a second guest-starring Emmy nomination. That year also saw her returning home to ABC, where she was visible on two of its highest-rated shows, the medical drama "Grey's Anatomy" (2005-) and the soap drama, "Desperate Housewives" (2004-2012), on which she played Wisteria Lane's meddling neighbor Carolyn Bigsby. Metcalf was simply doing what she always did - challenging herself and returning to her frequent, welcoming collaborators. Proving this to be a sound philosophy, she racked up her third feature film with Garry Marshall, "Georgia Rule" (2007) and provided a voiceover in another of Disney's prominent animated films, "Meet the Robinsons" (2007). The following year, Metcalf was seen briefly as the mother of a fallen soldier (Quay Terry) in writer-director Kimberly Peirce's examination of the effects the Iraq War had on young servicemen and their families in "Stop-Loss" (2008). Back on television, she landed a starring role on the short-lived sitcom "Easy Money" (The CW, 2008-09). Although the show was cancelled after a mere eight episodes, Metcalf remained busy, lending her voice to the animated features "Persepolis" (2007), "Toy Story 3" (2010) and "Hop" (2011). At about the same time, she was once again working alongside her old "Roseanne" castmate Johnny Galecki in the recurring role of Mary Cooper, Sheldon Cooper's (Jim Parsons) mother on the hugely successful sitcom "The Big Bang Theory" (CBS, 2007-). In 2013, she began a recurring role as a doctor in the black medical comedy "Getting On" (HBO 2013-15). This was followed by a co-starring role on the situation comedy "The McCarthys" (CBS 2014-15), in which she played the matriarch of a close-knit Boston family. This short-lived series was followed by a guest role on Louis CK's low-budget streaming sitcom "Horace and Pete" (2016). Metcalfe returned to the big screen in Greta Gerwig's coming-of-age comedy-drama "Lady Bird" (2017), playing the often-exasperated mother of Saoirse Ronan's title character. Her first film role since "Toy Story 3" (2010), it garnered her an Academy Award nomination for Best Actress in a Supporting Role. The same year, it was announced that Metcalf would return to a rebooted "Roseanne." The series premiered to strong ratings in the spring of 2018, but just after the first season concluded, Roseanne Barr was fired for controversial comments she made on Twitter. The series was retooled as "The Conners" (ABC 2018-) for its second season.