Veteran buttoned-down LAPD detective Murtaugh is partnered with slightly unhinged, former Navy SEAL Riggs. The odd couple embark on their first homicide investigation as partners, involving a young woman known to Murtaugh with ties to a drug and prostitution ring.

Responding to a noise complaint at a party at heavyweight boxer Ronald Dawson's Hollywood Hills home, Riggs and Murtaugh are drawn into a major case involving illegal gun runners with advanced military technology.

Riggs and Murtaugh follow a violent case involving a drug cartel, theft, killings, and Murtaugh's old T.O., Ned Brower. As the case unfolds, it turns out Ned's more involved than just driving the cash, which leaves Murtaugh with an inevitably dangerous decision to make.

A string of burglaries hits close to home for Murtaugh when one occurs in his own neighbourhood, and it gets just as personal for Riggs when another break-in ends in a casualty.

Murtaugh delves deep into the psyche of a former Navy SEAL who is wanted for criminal activity, and draws parallels between him and his partner Riggs. Riggs' connection to the suspect threatens to interfere with the case, but it also forces him to open up to Murtaugh.

When Riggs and Murtaugh investigate a high-profile case surrounding the murder of a young model, they uncover a vicious secret behind the locked mansion gates of one of LA's wealthiest families. Riggs gets surprised when an old friend of his wife has ties to the case.