Minnesota had a five-game winning streak halted and dropped a game below 500, but stayed within 4 1/2 games of division-leading Detroit in the American League Central.
Guthrie (9-12) won his second straight start, striking out five without walking a batter.
Baltimore scored twice in the first, once on a throwing error by shortstop Orlando Cabrera, and Felix Pie added a solo homer in the fifth.
Chad Moeller drove in Baltimore's final two runs with a double in the sixth and a bases-loaded walk in the eighth.
Losing pitcher Nick Blackburn (8-9) gave up four runs on nine hits in 5 2/3.