After he graduated from high school, a move to New York to attend the Conservatory of Theatre Arts & Film at SUNY Purchase did not go as well as Hartnett had hoped, and a year later, at 19, he found himself in California. Shortly after arriving in Los Angeles, he caught an improbable break, landing a part in the short-lived but acclaimed drama Cracker, on ABC. Although the series was cancelled after sixteen episodes, Hartnett had made a name for himself. He then began to focus on feature film work. He performed in small plays and on national television commercials before being cast in his first feature film, playing the son of Jamie Lee Curtis’ character in Halloween H20: 20 Years Later. Released on August 5, 1998, it performed well at the box office.

Hartnett was chosen as one of Teen People magazine’s “21 Hottest Stars Under 21” in 1999, Teen People’s “25 Hottest Stars under 25”, and one of People magazine’s “50 Most Beautiful People”, both in 2002. He was also voted Bliss magazine’s “3rd Sexiest Male”, and in 2003 PETA named him the Sexiest Vegetarian Alive, as chosen by voters.

Hartnett developed a film career, having appeared in Hollywood films, including The Faculty, Black Hawk Down, Lucky Number Slevin and Pearl Harbor. He was originally scheduled to play the role of Tino in Deuces Wild, but dropped out to star in Pearl Harbor. In 2002, he starred in O, an adaptation of William Shakespeare’s Othello set in an American high school, as Hugo, the film’s version of Iago. In the early 2000s, Hartnett was approached several times to play the role of Clark Kent/Superman in the early 2000s for a project originally helmed by Brett Ratner, but always turned it down, not wanting to commit to a predicted ten-year role. Hartnett said of his decision, “It just wasn’t the kind of movie I wanted to do. I turned down other superhero roles as well.”

Among his 2007 roles were Resurrecting the Champ, a drama also starring Samuel L. Jackson, and the graphic novel-based 30 Days of Night, in which he played a small-town sheriff. Hartnett described the second film as “supernatural, but kind of a western”. He was going to play trumpet player Chet Baker in the film The Prince of Cool, but did not agree with the producer’s ideas and left the project.

Hartnett has been involved in various causes. In 2007, he took time out from filming to support the green lifestyle campaign of Global Cool.

In 2008, Hartnett played Charlie Babbit alongside Adam Godley in the theatre adaptation of Barry Morrow’s Academy Award-winning Rain Man at the Apollo Theatre in London’s West End. He starred in the new campaign of the Emporio Armani fragrance, “Diamonds for Men”, being featured in both print and TV ads for the fragrance, thus becoming the first male celebrity to represent Giorgio Armani Beauty.

In 2009, Hartnett produced the video clip for the rapper Kid Cudi’s song Pursuit of Happiness.

In 2011, Hartnett became one of a handful of celebrities attached to USAID and Ad Council’s FWD campaign, an awareness initiative tied to that year’s East Africa drought. He joined Uma Thurman, Chanel Iman and Geena Davis in TV and Internet ads to “forward the facts” about the crisis.

In 2012, Hartnett also joined Barack Obama in his campaign in Minnesota, appearing at such events as the Minnesota Greater Together Youth Summit before formally endorsing the President on the official campaign YouTube channel. He along with Minneapolis Mayor RT Rybak also appeared at the University of Minnesota’s McNamara Alumni Center for an Obama Q&A in April.

In 2013, Hartnett was a guest of honor on Off Plus Camera.

In 2014, he was cast in the part of Ethan Chandler in the Gothic horror series Penny Dreadful, shot in locations around Dublin and Ireland. Later Hartnett’s character turned out to be none other than Lawrence Talbot / the Wolfman, who had changed his name to distance himself from his family. Hartnett became the third actor to portray the Wolfman in big-budget production.