Farrell quickly vaulted to the A-list and soon found himself fielding offers for roles originally earmarked for stars like Jim Carrey, Matt Damon and Edward Norton. In 2001, he starred as Jesse James in the poorly received revisionist Western "American Outlaws" and was cast as a lawyer turned WWII pilot who is captured by the Germans and then must defend a fellow P.O.W. on murder charges in "Hart's War" (2002) opposite Bruce Willis. Farrell's major introduction to mainstream audiences came in 2002, when he acted alongside Tom Cruise (as the hard-nosed Danny Witwer, who doggedly pursues Cruise's character) in the Steven Spielberg-directed sci-fi thriller "Minority Report." His first major starring role in a studio release was set to be the Schumacher-directed "Phone Booth," but it was postponed from its original fall 2002 release date due to a series of similar, real-life sniper killings in Maryland making news at the same time. Despite the delay, by early 2003, buzz was high on Farrell--whose press interviews routinely featured the unabashed, outspoken actor drinking, smoking and cursing--as he starred in two high-profile films: first, "The Recruit," in which he played a rising young operative at the CIA who becomes embroiled in the mysterious machinations of his teacher (Al Pacino) and his lover (Bridget Moynahan); second, in memorable appearance as the comic book villain Bullseye, an assassin with incredibly deadly accuracy, who battles Ben Affleck in the big screen version of Marvel Comics' "Daredevil" (2003). Farrell went devilishly over-the-top as a comic book killer and makes the most of his all-too-brief appearances. The increasingly popular star next starred in the big-budget, action-oriented version of the 70s cop drama "S.W.A.T." (2003), playing a former S.W.A.T. team member thrown off the team in the aftermath of a controversial decision who gets a chance to redeem himself when he's recruited by team leader Samuel L. Jackson for a high-risk mission.

Farrell then surprised critics with an atypical performance in "A Home at the End of the World" (2004), playing the sweet-natured, soft-spoken Bobby, a man coming of age in the 70s and 80s who, after being taken in by a family following the death of his beloved older brother, is caught up in a unique family dynamic and romantic triangle as he tries to live up to his brother's hippie sensibilities. He followed up with a bravura performance, complete with dyed blonde hair, as Macedonian conqueror Alexander the Great in Oliver Stone's epic historical drama "Alexander" (2004). Alas, Farrell’s star turn as the conflicted conqueror failed to elevate the film into a hit—at least within the contiguous United States. Meanwhile, the actor starred in another historical drama made by an acclaimed director, Terrance Malick’s “The New World” (2005), a lyrical, but ultimately meandering take on the settlement at Jamestown, Virginia in 1607 and the ensuing love affair between Captain John Smith (Farrell) and a young Native American girl, Pocahontas (Q’Orianka Kilcher).

Farrell was next seen in “Ask The Dust” (2006), a project that finally saw fruition after being in development for over 30 years. Farrell was cast as a young, ambitious writer fled from Colorado because of his Italian heritage to Los Angeles where he flourishes as a novelist and becomes obsessed with a Mexican barmaid. Farrell was then set to film “Pride And Glory” (lensed 2006), a crime drama about the personal and professional lives of three generations of New York police officers. He was next cast by director Michael Mann to play Sonny Crockett in the remake of the hit 1980s police procedural, “Miami Vice” (2006). Shooting began in April 2005 and from the start the production experienced on disaster after another. Known to work his actors harder than most directors, Mann told Farrell to bulk up for his role. Farrell complied, but injured his back and ribs while lifting weights, pushing production back six weeks into the heart of hurricane season. Then while out joyriding in a convertible Ferrari with costar Jaime Foxx, who played partner Ricardo Tubbs, a strong wind blew out the windows on a skyscraper and sent large shards of glass onto the street below where the two actors were cruising around. They barely escaped unscathed.

After a grueling 105-day shoot that saw a local Dominican shot by Mann’s security after he brandished a gun near set, Farrell checked himself into a drug rehab for his growing dependence on prescription drugs. He completed the program successfully and took some much needed time off. Returning to the public eye in 2006, Farrell did the usual promotion for “Miami Vice” before moving on to film Woody Allen’s 2006 summer project in London, a comedy about two brothers (Farrell and Ewan McGregor) with serious financial troubles who are approached by a third party to commit a crime that goes bad and eventually turns them into bitter enemies.