His catcher, Salvador Perez, delivered the game-deciding hit, a two-run single off Ryan Dempster in the Royals' three-run fourth inning.
The game was played on a crisp but sunny 49-degree afternoon as the city of Boston strove to regain a sense of normal life after days of horror, chaos and uncertainty. This was the second baseball game played since the Marathon bombing and subsequent postponement of Friday night's game.
Once again, the strains of "Sweet Caroline" reverberated through the antique ballpark as a crowd of 31,483 enjoyed a second day of unrestricted activity after last Friday's area-wide lockdown.
The Fenway focus was on baseball and, after Alcides Escobar lofted a solo home run over the Green Monster in the first, Red Sox fans got revved up in their half. Successive singles by Daniel Nava, Dustin Pedroia and David Ortiz scored one run. Another came when second baseman Chris Getz dove for Mike Napoli's grounder and threw him out while Pedroia scored.
All the while, Santana was trying to warm his fingers and get a feel for the ball.
"It was tough. ... No good. ... That was a big problem," Santana said.
At least it was in the first inning. After that, he said, "I got a better feel and just finished every pitch up front and kept the ball down. That was the huge thing for me today."
First innings have been something of a problem for Santana in his last three starts, in which he's 2-0 with one no-decision. In those three games, opponents are 9-for-17 with four runs (three earned, for a 9.00 ERA) against him in the first inning. In the 20 innings after that, they're just 13-for-69, and his ERA is 0.45.
The Red Sox touched him for six hits, five of them in the first two innings, and at one point he retired 11 straight batters. He walked no one.
"When I don't give any walks, it gives me more opportunity to attack the zone and work more comfortably," Santana said.
It made him much more comfortable, too, when the Royals got those three runs in the fourth. Billy Butler and Eric Hosmer each singled, and Lorenzo Cain ripped an RBI double down the left-field line for a 2-2 score.
But there progress stalled, as Dempster struck out both Mike Moustakas and Jeff Francoeur with two runners perched in scoring position. Manager Ned Yost defended those at-bats.
"You go back and look at Francoeur's at-bat, and [the first two] strikes were painted on the lowest part of the strike zone on a pretty good curveball," Yost said. "And ... he struck Moose out on a split that was phenomenal -- it started at the knees and then dove away from him. The guy made clutch pitches in those situations."
Up came Perez, who had struck out his first time against Dempster, and who noted that the Red Sox were playing him to pull to left field.
"He thought I'd have the same approach, try to pull the ball," Perez said, "but I stayed in my approach and went up the middle."
His soft liner floated just over the glove of shortstop Stephen Drew.
"It was a huge, clutch at-bat, there's no minimizing that," Yost said. "After the way that Dempster pitched Moose and Frenchy, for Sal to get a ball up and get it into the outfield ... Well, it was a game-winner. A huge at-bat."
Kansas City's fourth run ended Boston's streak of 16 games in which no starter gave up more than three runs.
"Just didn't make a pitch. Needed to make a better pitch there," Dempster said. "I had an open base and a lot of room to work with, and he did a good job of going off the plate to get a slider there and hooking it into left field."
That was the end of the scoring, but not the end of the drama.
Left-hander Bruce Chen replaced Santana to start the eighth and got two outs, but gave up two singles. That prompted Yost to bring in right-hander Aaron Crow to face the right-handed-hitting Napoli, but Crow walked him, missing the plate on four straight pitches.
"He wasn't missing," Yost said archly.
Aha. Anyway, Crow went to 2-0 on the next hitter, Jarrod Saltalamacchia. Pitching coach Dave Eiland conferred with Crow, who promptly induced a soft tap back to the mound. End of inning.
"Eventually, you've got to throw a strike. Right?" Crow said.
The Royals tried to stir up an insurance run or two in the ninth, when Moustakas and Francoeur each singled, but the Red Sox came within a whisker of a 5-4-3 triple play, settling for a double play after Perez beat the throw to first base. Then Getz flied out.
Greg Holland, looking more like the closer of old, pitched a perfect ninth, with two strikeouts, for his fourth save.
Has anything changed with Holland?
"Just mind-set," Yost said. "Going into it, you forget how to close a little bit -- and it's 'OK, I've got to throw strikes, I've got to get ahead. My stuff's great, I'm just attacking you.' Once he figured that out -- dynamite."