The announcement came after the 32-year-old had seen his fair share of injuries with shoulder problems that limited him to making just six appearances on a big league mound since 2006.
But it wasn't always that way for Mulder, who emerged as one of baseball's premier left-handed pitchers when he was with the A's, including a breakout season as 23-year-old in 2001, when he finished second in the balloting for the AL Cy Young Award after winning 21 games while posting a 3.45 ERA in 229 1/3 innings pitched.
It began a stretch of dominance in Oakland for both Mulder and the A's, as he averaged 18 wins a season and a 3.65 ERA from 2001-04, while the A's averaged 98 wins and made three playoff appearances during that stretch. It was during those years in Oakland where Mulder really shined, along with two other young pitching sensations in Zito and Hudson.
"It was a great time for all of us," Hudson remembered. "We were all young. We are all experiencing being in the big leagues for the first time together. And we were all pretty damn good."
Mulder, who was selected by the A's as the No. 2 overall pick in the 1998 Draft, began his career with the A's in 2000 when he posted a 5.44 ERA in 27 starts as a rookie. Oakland began a streak of four consecutive playoff berths that season but Mulder didn't pitch in the postseason because of a back injury he suffered in September.
But it was in 2001 when the "Big Three" officially arrived, as Mulder bounced back in a big way to combine forces with Zito and Hudson to form one of the best pitching trios in baseball.
Together they combined to win 58 games with a 3.43 ERA to lead the A's to a 102-win season that saw them win the Wild Card before losing the AL Division Series in heartbreaking fashion to the Yankees in five games despite being up, 2-0, in the series.
The A's repeated their success over the next two seasons by riding their three-headed monster to back-to-back division titles. Mulder remained a big part of that success by winning a combined 34 games over those two years with a 3.31 ERA and was also selected to the All-Star team for the first time in his career in 2003.
"He had unbelievable stuff," Hudson said of the 6-foot-6 Mulder. "He had the best stuff, in my opinion, on our staff -- on a staff that was one of the best staffs in baseball."
But even with that staff, the A's couldn't use it to their advantage in the postseason, as they never advanced out of the first round despite that impressive trio atop the rotation.
Mulder, though, wasn't to blame. He had a combined 2.25 ERA in the playoffs in '01 and '02 before missing his second postseason in '03 with a stress fracture in his right femur that ended his season in August.
The next season, however, would be the last of the "Big Three" in Oakland, as the club missed the postseason in '04 and both Hudson and Mulder, who were both All-Stars that year, were traded after the season.
Hudson was sent off to his hometown Atlanta Braves while Mulder was shipped to St. Louis for a horde of talented prospects, including current A's first baseman Daric Barton, current D-backs ace Dan Haren and reliever Kiko Calero, who recently signed with the Dodgers organization.
Mulder didn't let the trade faze him. He picked up where he left off in his first season with the Cardinals in '05, winning 16 games with a 3.64 ERA. He shined in the playoffs with a 2.45 ERA in three starts as St. Louis advanced to the NL Championship Series before losing to the Astros in six games.
Little did Mulder know, however, was that his next three seasons would be injury-riddled and that he would throw his last big league pitch in '08 at just 30 years old.
It started with season-ending rotator cuff surgery in September 2006 after posting a 7.17 ERA in 17 starts, which also forced him to miss the Cardinals' surprising run to the World Series title that season. He still signed an incentive-laden deal for two years and $13 million to remain with the Cardinals for the next two seasons but went 0-3 with a 12.08 ERA in six appearances, including just four starts, to finish his career.
But his Cardinals teammates had nothing but respect for him because of his work ethic and attitude despite his various injuries, which ended his nine-year career with a 103-60 record and 4.18 ERA.
"Obviously he had the injuries that hurt him a lot, but for a while he was one of the premier lefties in the league," said Cardinals infielder Aaron Miles, who was Mulder's teammate in St. Louis from '06-07. "He was just a real professional. Went about his business the right way. He studied the opponents well and was very prepared. He was a big-time pitcher in this league for a long time."
Cardinals veteran right-hander Jeff Suppan, who pitched alongside Mulder while with St. Louis in '05-06, also had only positive things to say about his time with Mulder.
"He was a great teammate," Suppan said. "He had to go through a lot of challenges. I wasn't here for a lot of them, but any time, that's a tough decision. I wish him the best. He was a great pitcher."
It appeared to be an especially difficult decision to retire for Mulder, who nearly attempted a comeback with the Brewers this past offseason to reunite with former A's pitching coach Rick Peterson. But the move never materialized and Mulder waited until Tuesday to finally make an announcement on his future.
It's never easy to hang up the spikes, and his former A's teammate Eric Chavez, who has been having his own thoughts of an early retirement because of injuries, empathized with Mulder and his situation.
"I know one thing for sure was that if Mark didn't feel right, he wasn't going to come back," Chavez said. "He wanted to come back 100 percent and didn't want to suffer like he has been the last couple of years. Once you've played a game at a certain level and dominated, it becomes a lot tougher to come back. You want to tap into your abilities and know you can still perform well. He wasn't going to do it if he knew he couldn't be successful and contribute."
Mulder, though, can now focus his energy on golf, and much like he did while he was on the mound, he's seeing plenty of success, winning six of the nine amateur events he's entered as part of the Golf Channel Amateur Tour.
But even if Mulder continues his success as a golfer, after his baseball career he'll still always be remembered most for being one of baseball's best left-handers in his days as part of Oakland's vaunted "Big Three."
"Just that combination was pretty special" said a nostalgic Hudson. "It doesn't happen often. It was a time in my life, I think back on it and I just start smiling."
But even with his premature ending to his career, there's no doubt Mulder can look back with a smile, too.