Harlin moved to the U.S. in the mid 1980s and initially started directing low-budget films. Harlin gained attention after directing A Nightmare on Elm Street 4, which proved to be a success. His next film, the Andrew Dice Clay film The Adventures of Ford Fairlane failed at the box office, but Harlin achieved financial success with Die Hard 2.

He revived the career of Sylvester Stallone with the 1993 hit Cliffhanger but 1995's infamous Cutthroat Island proved to be such a box-office flop that the company that produced it, Carolco, went out of business soon afterwards. Harlin was set to direct the film Alien³ and worked on it for over a year but later backed out due to dissatisfaction with the script.

Harlin married actress Geena Davis in 1993 and, interestingly, he cast her as the lead in some of his films, including Cutthroat Island and The Long Kiss Goodnight. They were later divorced in 1998 and in interviews Davis has been critical of the effect her relationship with Harlin had on her career (and the universally negative reviews on Cutthroat Island and The Long Kiss Goodnight lend credence to this). It was Stallone who helped Harlin out by giving him the film Driven but this proved to be only a mild success, basically because many critics thought Stallone's script was depressingly cliché-ridden and unrealistic.

In 1993 Harlin directed the TV-show American Gladiators for finnish TV. Former pro-wrestler Tony Halme, stagenamed Ludvig Borga, starred as gladiator named Viikinki (English: "viking").

The film Exorcist: The Beginning, the prequel to the Exorcist film series, was initially directed by Paul Schrader. Reportedly, the studio was dissatisfied with the resulting film: a brooding and psychological look at exorcism that lacked the blatantly horrific scenes of the first movie. Schrader was fired and the film was totally re-shot by Harlin, ostensibly to create a version of the film closer to traditional horror movie expectations. Following fan pressure Schrader's film was released on DVD and received better fan critical response than Harlin's version.

His style is fast-paced and rhythmically engaging. His better action films Long Kiss Goodnight, Cliffhanger and Die Hard 2: Die Harder showcase a visual and technical talent greatly above average Hollywood action directors.

He is now attached to a number of movies including the comic book adaptations The Covenant and Full Moon Fever, the viking adventure The Northman and the action film Run.