Born in Edgerton, Wisconsin, Stricker grew up playing golf at both Lake Ripley Country Club in nearby Cambridge and at the Edgerton Towne Country Club in Edgerton. A 1990 graduate of the University of Illinois, Stricker earned All-American honors as a member of the Illini golf team in 1988 and 1989.

Stricker turned professional in 1990 and began his career on the Canadian Professional Golf Tour, where he won two tournaments. He joined the PGA Tour in 1994, and his first success at the top level came in 1996, when Stricker notched two victories (Kemper Open, Motorola Western Open) and seven top ten finishes on his way to finishing fourth on the 1996 PGA Tour money list.

In 1998, Stricker played himself into contention in the final round of the PGA Championship at Sahalee Country Club near Seattle. Thanks to a back-nine surge, PGA Tour veteran Vijay Singh bested Stricker down the stretch and claimed a two-stroke victory. This runner-up finish remains Stricker’s best result in a major championship to date. Stricker has finished inside the top-20 six times at the U.S. Open, with his best finish a fifth-place in 1999 at Pinehurst No. 2. He won his third and most prestigious PGA Tour title at the WGC Match Play Championship in 2001, where he defeated Pierre Fulke 2 and 1 in Australia, to earn the $1,000,000 prize. This remains as the only time that the WGC Match Play Championship was played outside of the United States.

At the start of the 2013 season, Stricker announced he would cut his schedule “in half,” hoping to play just “10 or 12” tournaments. As the defending champion, he finished runner-up at the Hyundai Tournament of Champions despite suffering from a herniated disc. He then reached the quarterfinals at the WGC-Accenture Match Play Championship, his best performance since his victory in 2001.

Stricker lost his tour card in 2004. At age 39 in 2006, relying on sponsor exemptions, he managed seven top-ten finishes and was voted the tour’s Comeback Player of the Year. In 2007 he won his fourth PGA Tour title at The Barclays on August 26, ending an 11-year victory drought on American soil, although he had previously triumphed down in Australia in 2001. This run of success earned him a spot on the Presidents Cup team in 2007.

After his victory at The Barclays, which was the first of the four FedEx Cup playoff events, Stricker reached No. 4 in the Official World Golf Ranking, his highest career ranking at that point. Stricker finished runner-up in the 2007 FedEx Cup Playoffs behind Tiger Woods, and was again selected as Comeback Player of the Year. He was also inducted into the Wisconsin State Golf Association Hall of Fame in 2007.

At the Bob Hope Classic in January 2009, Stricker shot third and fourth round scores of 61 and 62, at the PGA West Palmer and Nicklaus courses, to set the 36-hole scoring record on the PGA Tour at 123, beating a record that Pat Perez had held for only two days. (This record fell in October when Troy Matteson shot 61-61=122 at the Frys.com Open.) His four-round total of 33-under-par in the five-round event also set the PGA Tour record for lowest score relative to par for 72 holes, exceeding Ernie Els’ total of 31 under par in the 2003 Mercedes-Benz Championship at Kapalua. The third-round 61 was Stricker’s best score on tour to that point, but a 77 in the final round dropped him into a tie for third.

In February 2010, Stricker won his eighth tour title at the Northern Trust Open with a 16-under-par 268 winning total. With this win at Riviera, he passed Phil Mickelson and regained his ranking as World No. 2.

In June 2011, Stricker won at the Memorial Tournament in Ohio, his tenth tour title. He opened with 68 and bettered this with 67 in the second round. However, this was made special by the hole-in-one he recorded at the par three 8th hole to hold a three stroke advantage at the halfway stage. Remarkably, he then opened round three with two eagles in the first five holes to open up a six-shot lead midway through round three, but some uncharacteristic mistakes on the back nine saw him fall back towards the rest of the field. He held on to the 36-hole lead to eventually win by one stroke over runners-up Matt Kuchar and Brandt Jobe. With this victory, Stricker became the highest-ranked American in the Official World Golf Ranking, at fourth in the world. For the first time in his career, 44-year-old Stricker was ranked higher than all other American golfers, including Tiger Woods and Phil Mickelson. Stricker played the tournament at −20 for the front nine, a record by 6 shots, versus +4 for the back nine.

Stricker tied a major championship record with a 63 in the first round at the PGA Championship in 2011, and led by two shots. His next three days were 74-69-73, and he tied for twelfth. Stricker’s career earnings are over $44 million through the end of the 2018–19 season, among the highest of those without a major title.

In 2017, Stricker joined the PGA Tour Champions. In his first event, the Tucson Conquistadores Classic, he finished one stroke behind Tom Lehman. Stricker asked the USGA for a special exemption to play in the 2017 U.S. Open held in his home state, but his request was denied. He eventually earned entry through a qualifying tournament in Memphis. Stricker was the captain of the victorious U.S. team in the 2017 Presidents Cup.

In March 2018, Stricker won his first event on the PGA Tour Champions, the Cologuard Classic by two strokes. He then won his second straight start at the Rapiscan Systems Classic in Saucier, Mississippi. In September 2018, he won the Sanford International tournament on the PGA Tour Champions.

In 2018, U.S. captain Jim Furyk named Stricker as a non-playing vice-captain for the 2018 Ryder Cup team. The U.S. lost 17 1/2 to 10 1/2 to the European team.

In 2019, Stricker won his first senior major championship at the Regions Tradition, claiming a six stroke win over the field. Then in June of the same year, Stricker won his second senior major at the U.S. Senior Open, again by six strokes over Jerry Kelly and David Toms.