With Brendan Donnelly (2-1) on the mound, Guillen drilled a 2-0 fastball over the right field wall for the win.
Johnny Damon went 3-for-5 with a run scored for the Tigers, who have taken the first two games of this set. Phil Coke (4-0) got the win for throwing the 10th while Jeremy Bonderman went seven innings in the start, giving up two runs on six hits with a walk and six strikeouts.
Garrett Jones hit a solo home run and scored twice while Ryan Church and Neil Walker each drove in a run for Pittsburgh, which has lost seven straight. Paul Maholm went six innings and was charged with just one run on eight hits with three walks and two strikeouts.