In the spring of 1957 newly qualified midwife Jenny Lee arrives in the East End of London to begin her career. After overcoming the initial shock that her new home, Nonnatus House, is a convent rather than a private hospital she quickly becomes immersed in her new life. Living with Nuns and working in a community of colorful characters, such as Conchita Warren and her 25 pregnancies, is different from anything Jenny has encountered previously. Through her we experience the sorrows and joys which come with being a midwife.

As Jenny Lee settles into her role, there is a new arrival at Nonnatus House, Chummy (Miranda Hart). A welcome pair of extra hands Chummy sets about showing her worth, but an overwhelming keenness to please and her inability to ride a bike prove obstacles in gaining the respect of Sister Evangelina. Meanwhile a chance encounter with Mary, a young pregnant runaway, forces Jenny to see an unfamiliar darker side of life.

Jenny is placed on the district nursing roster for a few weeks, to extend her experience of community practice. During her rounds she attends to Joe, a gentle old soldier, and a friendship forms. At the antenatal clinic Trixie and Cynthia enrol Winnie Lawson as new patient. In her forties Winnie had thought her days of nappies and babies were long gone, and seems upset by her pregnancy. By contrast her husband Ted is overjoyed by the news. However at the baby's birth everyone gets a bit of a surprise.

A baby girl, recently delivered by Jenny, is snatched from her pram, causing great anguish to her family and uniting the local community as they search for the missing child. Meanwhile Cynthia witnesses another type of loss as she assists in the case of soon-to-be parents David and Margaret. Newly married and excited about their future, everything is put in jeopardy when Margaret develops eclampsia.

When Peggy’s brother is diagnosed with cancer, Jenny and the nuns are called upon to care for him. Jenny gets to know the siblings better. The Nonnatus House residents get involved in Fred’s latest money-making scheme which involves a pig called Evie.

When Chummy's imperious mother visits and disapproves of Peter Noakes, Chummy defies her mother and has her wedding on her own terms. Senile Sister Monica Joan is arrested for shoplifting.