Colon, 40, gave up three first-inning runs in his first post-season appearance in eight years. He blanked the Tigers the rest of the way through a six-inning effort, but his teammates could not overcome their early deficit.
Scherzer, who led the majors with 21 victories this season and who won his final four starts of the regular campaign, shut out Oakland through six innings before giving up a leadoff, infield single in the seventh to Brandon Moss and a home run to Yoenis Cespedes.
Two Detroit relievers protected the one-run lead through the final two innings, preserving a win to open the best-of-five American League Division Series. Oakland will host the second game on Saturday before the series heads to Detroit for contests on Monday and, if needed, on Tuesday.
Colon, whose rookie major league season came in 1997, was looking for his first playoff victory in a dozen years.
He came up short, however, due to a nervous start in which the first three batters he faced reached base.
Austin Jackson opened the game with a double and Colon then hit Torii Hunter with a 1-0 pitch. Miguel Cabrera quickly took advantage with a single to center that scored Jackson and moved Hunter to third.
Prince Fielder followed by grounding into a double play that brought home Hunter with the second run of the inning.
Scherzer allowed only three hits and struck out 11 in his seven innings. Two of the hits came from Cespedes -- a one-out triple in the second that failed to lead to a score and the two-run homer in the seventh.
Drew Smyly recorded two outs in the eighth and walked one before Joaquin Benoit came on for a four-out save. He struck out the side in the ninth, giving Detroit pitching 17 strikeouts for the game.