Colon ended Santana's 17-game winning streak by allowing just two hits in 7 1/3 scoreless innings of the Angels' 2-1 victory over the Twins on Sunday afternoon.
"The only way to beat good pitching," Los Angeles manager Mike Scioscia said, "is with good pitching."
Santana (4-1) allowed only two hits himself, equaling his career low, but they were homers by Vladimir Guerrero and Jose Molina. The AL's reigning Cy Young Award winner struck out seven over eight innings yet lost for the first time since last July 11, a span of 21 regular-season starts.
"It doesn't mean the fun's over. We're still working," Santana said as Latin music played loudly on the clubhouse stereo, a custom after his outings.
Santana's previous two-hit game, coincidentally, was also his last loss -- a 2-0 decision to the Detroit Tigers at the Metrodome right before the 2004 All-Star break.
"We knew if Johan's streak was going to be broken, it was probably going to be in one of these -- where we couldn't score many runs off their guy," Minnesota manager Ron Gardenhire said.
Colon (4-2) had no such streak. Alex Rodriguez hit three homers and the Yankees scored 10 runs against him over 3 2/3 innings in New York earlier this week.
But Colon was sure ready for this one, retiring the first nine batters in order -- all on groundouts. Shannon Stewart's line-drive single leading off the fourth inning was the first ball to leave the infield.
Lew Ford was the only other player to reach base until the eighth, on a fielder's choice grounder to third that forced Stewart out at second. Colon set down the next 11 hitters, leaving after an infield single by Jacque Jones with one out in the eighth.
"In New York, it was not my day," Colon said through an interpreter. "Today, it was my day."
Colon tried to glove the high chop hit by Jones with a jump off the mound, but the 5-foot-11, 250-pound right-hander appeared to land a little awkwardly on the artificial grass and sprained his left ankle. He was removed for Scot Shields.
"I thought it would be worse, but once I started walking around again it started to feel better and better," Colon said, noting he expects to make his next start.
In came closer Francisco Rodriguez, and pinch-hitter Matthew LeCroy grounded into a double play. Stewart hit his second homer of the year leading off the ninth, but Rodriguez retired the next three batters for his sixth save in seven chances.
Colon struck out seven, walking none.
"Sometimes you have to tilt your hat," said the Twins' Torii Hunter. "I hate to do that, but we have to tip it today."
Santana was nearly as dominant, save for two pitches. Guerrero, homering for the first time in 11 games, sent a flat 1-0 changeup soaring with that powerful uppercut swing of his in the fourth. The ball hit two-thirds of the way up the left field foul pole, which in this stadium is just a thin yellow net.
Molina's home run was his first and just his seventh hit of the year. He hit Santana's first pitch of the sixth inning into the left field seats to make it 2-0. Molina is 2-for-16 on this road trip.
"That's the way it is," Santana said. "You make mistakes, even though it doesn't look like it, you have to pay for it."
The Angels were glad to get away without being swept. Ending Santana's streak didn't matter.
"We were trying to win the game," Molina said. "We don't even care who was on the mound."
Angels third baseman Lou Merloni sprained his right ankle while awkwardly fielding Ford's grounder in the fourth. Replaced by Dallas McPherson, Merloni will be re-evaluated on Monday. ... Santana walked two, giving him just five for the season. ... Twins catcher Mike Redmond, playing for the first time in 10 days following a home plate collision that left him with bruised ribs, caught two men trying to steal and has thrown out four of six runners this year. The Angels lead the majors in stolen bases.