In the pilot episode, in the beginning when we see Riggs's wife, Miranda, wave to the next-door neighbor watering his lawn, the house behind him is the house the Murtaughs lived in from the Lethal Weapon films.

In the last episode of Season 1 during the graduation, one name is called out. Michael Waynes Kyle. A play on on Damon's character from My Wife and Kids, Michael Kyle

In the pilot, Roger Murtaugh is said to have recently celebrated his 50th birthday. Damon Wayans turned 56 the month the pilot aired. Danny Glover was only 41 when the original movie premiered in 1987. Keesha Sharp, who plays Trish here is 13 years younger than Wayans, whereas Darlene Love, who played Trish in the movie was 8 years older than Glover. Mel Gibson was 31 in 1987, whereas Clayne Crawford was 38 as of the air date of the pilot.

The series premiered 29 years after Lethal Weapon (1987).

Damon Wayans, who plays Murtaugh, was the protagonist of The Last Boy Scout. Both The Last Boy Scout and the original Lethal Weapon film were written by Shane Black, meaning this is the second time Damon Wayans has played a Shane Black character.

Advertisements for this series credited Clayne Crawford as "Introducing Clayne Crawford" (a credit usually reserved for actors making a debut) even though Crawford had his first onscreen credit in 1997 (in an episode of "Buffy the Vampire Slayer") and has multiple credits per year, every year, since the early 2000s.

In April 2018 Deadline Hollywood's Nellie Andreeva reported that negotiations for the show's third season renewal were being complicated by an ongoing problem with Clayne Crawford's on-set behavior. Andreeva reported that Crawford (Martin Riggs) had been repeatedly reprimanded for creating an emotionally abusive and hostile work environment and that the issue had "escalated to a point where other actors as well as crew on Lethal Weapon would feel uncomfortable being on set with him." Andreeva wrote that because past disciplinary action had not resulted in Crawford remediating his behavior, the showrunners were taking the very unusual step of considering the recasting of his role. After its publication in Deadline Hollywood, this story was picked up and republished in many other entertainment news outlets, including TV Guide, Vulture, TV Line, and others. In May 2018, Crawford was replaced by Seann William Scott.

The Captain is named for Avery Brooks.

Golden Brooks was replaced by Keesha Sharp for the role of "Trish Murtaugh".

In episode 9, Jingle Bell Glock, the opening scene of a girl falling from a building to her death onto a car, and that the episode takes place during Christmas time, comes straight from the first Lethal Weapon film.

In the third episode of season one, thieves rob an armored truck in almost the same method as the thieves from the film Heat (1995). Coincidentally, Ted Levine plays the armored truck driver in this episode, he also appeared as Bosko, one of the policemen on Al Pacino's squad in Heat.

Steve Boyum, one of the directors, performed stunts on the second and third films in the Lethal Weapon franchise. He also performed stunts in Forever Young, another film starring Mel Gibson, and The Last Boy Scout starring Bruce Willis and Damon Wayans, which was also written by Shane Black, along with the first Lethal Weapon film.

In the final episode of season 1, Riggs referred to Murtagh (Damon Wayans) as being bulletproof several times. In 1996, Wayans starred alongside Adam Sandler in a movie called, "Bulletproof".

Sean William Scott will replace the role of Martin Riggs with a new character starting in Season 3, after Clayne Crawford was fired due to his behavior on set.

Riggs' military background changes for the TV series from the film version. In films, Riggs (Mel Gibson) is a former U.S. Army Special Forces Sniper (i.e. "Green Beret"). In the TV series, Clayne Crawford's Riggs character is a former Navy SEAL.

Episode 9 is titled Jingle Bell Glock. This is a parody of the song Jingle Bell Rock that was played over the opening credits of the first film.

Clayne Crawford was fired from the series due to multiple onset reprimands and will not return for season three. Sean William Scott cast to replace him but it is unknown if he will assume role of Martin Riggs or a new character altogether .

Throughout the series, there are nods, some subtle and some overt, to the Lethal Weapon films.

While many aspects of the characters and the story lines have been subtly altered between the films and the series, the one constant is the death of Riggs' wife. In both the films and the series, it is established that she was killed in a car accident while Riggs was on the job. And in both mediums, it is later revealed that she was actually murdered.

In season 2 episode 4 the plane robber is named Dan Cooper, the actual name used in the D.B. Cooper highjacking in 1971. Commonly mistaken as D.B. Cooper but the skyjacker actually boarded as Dan Cooper.

In the season finale during the graduation scene they announced Michael Kyle Jr as a graduate which is his characters (Michael Kyle) son's name in the show My Wife and Kids

In season 2, episode 12, Riggs shoots a fish tank exactly like he does in the second movie and even says the line "you outta get these guys in some water" just like in the movie. There are lots of references like this, like when Riggs drives his car into Martaugh's living room at the end of season 1 which is like the end of the first movie.