The series is a television adaptation of Luc Besson's 1990 French film Nikita, created for TV by Joel Surnow and Robert Cochran and co-produced by Fireworks Entertainment and Warner Bros. Domestic Television Distribution.

Unlike the original film and its American remake Point of No Return, in which Nikita is a drug-addicted killer, the TV series makes her an innocent homeless young woman falsely framed for a police officer's murder, fundamentally changing the character's moral starting point.

In a key mission mirrored from the films—killing a VIP in a crowded restaurant—the film versions of Nikita complete the assassination, whereas the TV series' Nikita avoids killing the target during her first assignment.

La Femme Nikita was the number-one Nielsen-rated drama on American basic cable for its first two seasons, but lost network support after Barry Diller took control of USA Network in 1998 and replaced president Rod Perth with Stephen Chao.

During season three, network president Stephen Chao reportedly asked producers to cast professional wrestlers in terrorist roles to cross-promote WWE broadcasts on USA Network, despite the shows having incompatible audiences.

After its 2000 cancellation, fans organized the 'Save LFN' campaign, sending over 25,000 letters—including dollar bills bearing images of Roy Dupuis and Nikita's signature sunglasses—and taking out a full-page ad in The Hollywood Reporter, which helped convince USA Network to greenlight a truncated eight-episode fifth season.

Actor Matthew Ferguson played both Seymour Birkoff and his previously unknown twin brother Jason Crawford after the character's backstory revealed he was one of twin boys separated for a Section One psychological experiment.

The Season Two DVD box set was delayed roughly two years due to a music licensing dispute over the song 'Loaded Gun' by Hednoize used in the episode 'Off Profile'; a small number of sets containing the original song were released before being pulled and replaced, making them sought-after collector's items.

The show's title theme was composed by Mark Snow, while composer Sean Callery, who won an Emmy for his work on the series, released a limited promotional CD of his orchestral score at a fan convention in 2001.