Shortly after his 50th birthday, LAPD Homicide Sergeant Roger Murtaugh is partnered with Sergeant Martin Riggs, a transfer from narcotics. Riggs is a former Special Forces soldier who lost his wife in a car accident three years prior, has turned suicidal, and has been taking his aggression out on suspects, leading to his superiors requesting his transfer. Murtaugh and Riggs quickly find themselves feuding with each other.

The film holds a score of 84% on Rotten Tomatoes based on 51 reviews; the average score is 7 out of 10. The site's critical consensus reads, "The most successful installment in a phenomenally successful franchise, Lethal Weapon helped redefine action movies for the 1980s and 1990s". Audiences polled by CinemaScore gave the film an average grade of "A" on an A+ to F scale.

Michael Kamen, who just completed work on Highlander, composed the score for Lethal Weapon. The guitar part of Riggs' theme was performed by Eric Clapton. Kamen and Clapton had worked together on the music for the 1985 BBC TV series Edge of Darkness (the feature adaptation of which would later, by coincidence, star Mel Gibson). The saxophone part of Murtaugh's theme was performed by David Sanborn. The Christmas song "Jingle Bell Rock", performed by Bobby Helms, is played during the film's opening credits. Honeymoon Suite's song, "Lethal Weapon," is played during the film's end credits without being credited.

Both actors were signed by early spring 1986. Gibson and Glover then flew home to pack, and, returning to Los Angeles, began an intensive two months of physical training and preparation. Meanwhile, the crucial role of Joshua was settled when Gary Busey asked for a chance to read for the part. An established star since his Academy Award-nominated performance in The Buddy Holly Story, Busey had not auditioned for a film in years. "I had butterflies," he said. "I'd never played a bad guy. And no one had seen me since I'd lost 60 pounds and got back into shape. But I decided to take the initiative in order to have the opportunity to work with Dick, Joel, Mel and Danny. I'm constantly looking for someone to pull the best performance out of me and any of those guys could. They even talked me into dyeing my hair!" In his E! True Hollywood Story biography, Busey says he was hired to play Joshua because they were looking for someone big and menacing enough to be a believable foe for Mel Gibson. Busey also credits the film for reviving his failing film career.

Released on March 6, 1987, Lethal Weapon was No. 1 at the box office for three weeks before Blind Date supplanted it. It grossed $120.2 million worldwide and was nominated for the Academy Award for Best Sound Mixing (Les Fresholtz, Dick Alexander, Vern Poore and Bill Nelson) (losing to The Last Emperor). It is widely considered to be one of the best buddy cop films of all time, influencing numerous "buddy cop" films such as Tango & Cash, Bad Boys and the Rush Hour series.

Lethal Weapon has been released on VHS and DVD numerous times, along with a single Blu-ray Disc release. The first DVD was released in 1997 and featured the film's theatrical version. The Director's Cut was released in 2000. Since then, numerous sets have been released that contain all four films in the series (featuring the same DVDs). The theatrical version was also released on Blu-ray in 2006.

Mel Gibson was invited by Richard Donner as he was interested in working with the actor after Ladyhawke. Casting Director Marion Dougherty first suggested teaming Gibson with Danny Glover, given Murtaugh had no set ethnicity in the script. She arranged for Gibson to fly in from his home in Sydney while Glover was flown in from Chicago, where he was appearing in a play, to read through the script. According to a June 2007 Vanity Fair magazine article, Bruce Willis was considered for the Riggs role. This is referenced in the spoof of the Lethal Weapon films, Loaded Weapon 1. Bruce (as John McClane) appears after the villains attack the wrong beach residence, looking for the protagonist.

On January 19, 2011, Warner Bros. announced plans to reboot the Lethal Weapon franchise without Gibson and Glover. The new franchise was set to feature the same characters but a brand new cast. Will Beall was hired to write the script. A television version premiered in September 2016 on Fox starring Clayne Crawford as Martin Riggs and Damon Wayans as Roger Murtaugh.

Cedric Adams was the first expert brought in. "Adams thought the best possible way to show just how lethal Riggs really is — is to show his mastery of a form of martial arts never before seen onscreen," said Donner. Adams taught the actors the movements of Capoeira. A second technical advisor, Dennis Newsome, brought jailhouse rock to the fight sequence. The third technical advisor was Rorion Gracie, who specialized in Brazilian Jiu-Jitsu.