DiMarco turned professional in 1990, won the Canadian Tour’s Order of Merit as its money leader in 1992, and finished ninth on the second-tier Nike Tour in 1993 to earn his PGA Tour card for 1994. However, he was not always able to maintain his place on the PGA Tour, and he won his first professional tournament on the Nike Tour at the 1997 NIKE Ozarks Open. As he moved into his 30s, he continued to improve, capturing his first trophy on the PGA Tour at the 2000 SEI Pennsylvania Classic.
His second PGA Tour victory was the 2001 Buick Challenge, where he sank a 15-foot (4.6 m) birdie on the 18th hole to tie leader David Duval, and then won on the first hole of a sudden death playoff. He won his third PGA Tour event at the 2002 Phoenix Open, which featured an infamous moment—as DiMarco was addressing a pressure putt at TPC Scottsdale’s 16th hole, one of the fans yelled “Noonan!” (a reference from the movie Caddyshack). DiMarco maintained his concentration and sank the putt, then pointed at the fan and demanded that a tournament official eject him. By 2004, he had finished in the top twenty on the PGA Tour money list for five straight seasons, and had tied for second in the PGA Championship, losing the title to Vijay Singh in a three-way playoff. In 2005, DiMarco lost a sudden-death playoff with Tiger Woods to finish second in The Masters. The Masters result moved him into the top ten of the Official World Golf Rankings. DiMarco finished as the runner-up in a major for the third time at the 2006 Open Championship at Hoylake; Tiger Woods beating him by two strokes. DiMarco achieved his four-round score of 70-65-69-68 (272, −16) less than three weeks after the death of his mother.
Arguably, DiMarco enjoyed his most consistent success from 2002 to 2006, when he was ranked in the top ten of the world rankings for 61 weeks, going as high as number six in the world in 2005. DiMarco was also a member of the U.S. national team in the 2003 and 2005 Presidents Cup, and the Ryder Cup competitions in 2004 and 2006. DiMarco sank a 15-foot (4.6 m) putt to beat Stuart Appleby and clinch the 2005 Presidents Cup.
In 2007, he disclosed that he was suffering from a chronic shoulder injury, and underwent arthroscopic surgery on his left shoulder later that year. Notwithstanding the injury, DiMarco still finished among the top 25 in six tournaments and earned more than $950,000 in fewer than nine months in 2007.
DiMarco has not played a full PGA Tour schedule since 2012. He is a frequent contributor to Morning Drive on Golf Channel.