The character of Detective Robert Goren (Vincent D'Onofrio) is based on the popular fictional character of Sherlock Holmes, but instead of relying upon physical evidence like Holmes, Goren focuses on psychology to identify the perpetrators, whom he often draws into confessing or yielding condemning evidence. Goren also works with a John Watson like partner in Detective Alexandra Eames (Kathryn Erbe) and works for Inspector Lestrade type commanding officers Captain James Deakins (Jamey Sheridan) and Captain Danny Ross (Eric Bogosian) The character of Nicole Wallace (Olivia d'Abo) is a direct attempt to play on the part of Sherlock Holmes' female antagonist Irene Adler, also known as "The Woman". Wallace is employed as a "Professor of Literature" during her first appearance, which could be a parallel to Holmes' nemesis Professor Moriarty.

At the end of the fourth season, Jamey Sheridan suffered Bell's palsy, a facial paralysis that affected one half of his face. In the fifth season, his character, Captain James Deakins, carried an eye patch over his left eye, to hide the signs of the paralysis.

This is the only New York City-based Law & Order series in which Sam Waterston (Jack McCoy) and Richard Belzer (John Munch) did not appear.

Kathryn Erbe's real-life pregnancy was incorporated into the show's plotline, by having her character be a surrogate mother, carrying her brother's child.

To add a vulnerability to Goren's seeming invincibility, a backstory was added in which his mother was diagnosed as a schizophrenic during his adolescence.

Vincent D'Onofrio's contract was for seven consecutive years on the show.

Olivia d'Abo's fate as a recurring villain was once held in the balance by a phone-in poll. An overwhelming majority of fans voiced their desire for her to get away again.

Alexandra Eames once mentioned dating a man named "Terry", possibly a reference to Kathryn Erbe's real-life husband, Terry Kinney.

Vincent D'Onofrio and Kathryn Erbe previously guest starred in episodes of Homicide: Life on the Street (1993), which crossed over with Law & Order (1990).

The following statement appears at the beginning of each episode: "In New York City's war on crime, the worst criminal offenders are pursued by the detectives of the Major Case Squad. These are their stories." This is the only Law & Order series where the opening statement does not begin with the words "In the criminal justice system..."

Uses a re-mixed version of the theme music from Law & Order (1990), but a different re-mix than Law & Order: Special Victims Unit (1999). The episodes produced for the USA Network use the mix first heard on Law & Order: Trial by Jury (2005).

The show's format was partially inspired by Columbo (1971), starring Peter Falk. Both started out with the crime being seen from the criminal's point of view, and with them confident that they can get away with it. However, they then get outsmarted by a brilliant detective. The shows differ, in that Columbo (1971) usually showed the full crime in the beginning, while in this show, the viewer is only shown enough to be a few steps ahead of the detectives in knowing what happened. Goren and Columbo also have very different styles in analyzing the crime, and the suspects.

Beginning with season five, episodes' cast and opening credits alternate between Goran and Eames (Vincent D'Onofrio and Kathryn Erbe) and Logan and Barek (Chris Noth and Annabella Sciorra). In season six, Julianne Nicholson replaced Sciorra, and in season eight, Jeff Goldblum replaced Noth.

When Mary Elizabeth Mastrantonio joined the cast in season nine, her character was going to be named Sarah Brooks. At the last minute, producers decided to change it to Zoe Callas.

Chi McBride was considered for the role of Assistant District Attorney Ron Carver.

Vincent D'Onofrio and Chris Noth played the role of Phil Romano in That Championship Season, the former in the 1999 film, and the latter in the 2011 Broadway revival. In an earlier film version, the part was played by Paul Sorvino, Noth's co-star on Law & Order (1990).

The second spin-off of Law & Order. Law & Order (1990), Law & Order: Special Victims Unit (1999), Law & Order: Criminal Intent (2001), Law & Order: Trial by Jury (2005), Law & Order: UK (2009), Law & Order: LA (2010), and Law & Order True Crime (2017).

Bill Moseley was considered for the role of Captain James Deakins.

Jeff Goldblum and Vincent D'Onofrio appeared in the Jurassic Park film franchise. Goldblum was in Jurassic Park (1993), The Lost World: Jurassic Park (1997), and Jurassic World: Fallen Kingdom (2018) as Dr. Ian Malcolm. D'Onofrio was the villain, Vic Hoskins, in Jurassic World (2015).

While Chris Noth and Leslie Hendrix reprised their roles from Law & Order (1990), other actors and actresses appeared on both shows as different characters. This includes Courtney B. Vance, Eric Bogosian, and Julianne Nicholson.

Chris Noth (Mike Logan) & Leslie Hendrix (Dr. Elizabeth Rodgers) also worked together on The Good Wife (2009) & Law & Order (1990).

Chris Noth (Mike Logan) and Julianne Nicholson (Megan Wheeler) also appeared together in two episodes of The Good Wife (2009) together, as Peter Florrick & Callie Simko respectively.

The last Captain on this show, Jay O. Sanders, played a murderer in a previous episode.