Santana (9-9) tamed the Tigers on five hits, issuing one walk while striking out five.
Fielder led off with a walk against closer Greg Holland and, two outs later, Omar Infante stroked a potential score-tying double. But Royals left fielder Alex Gordon threw Fielder out at the plate to end the game and hand Holland his 43rd save.
Eric Hosmer's first-inning RBI triple supplied the only run for Kansas City, which came into the contest 3 1/2 games out of an American League wild-card spot.
Doug Fister (12-9) allowed one run on eight hits over 7 2/3 innings, walking four and fanning six for American League Central-leading Detroit.