Willingham tucked a two-run shot into the first row of seats beyond left-center field in the third inning for a 2-2 tie that Plouffe broke the next inning with a drive off the second-deck facing in left.
The home runs came off Rick Porcello (0-1) and helped Minnesota starter Mike Pelfrey (1-0) collect the win. Pelfrey was charged with both Detroit runs but both came as the result of Minnesota errors and were unearned. He allowed five hits and walked two over 5 1/3 innings.
After the Twins' home runs wiped out that lead, Minnesota put the game away with a five-run eighth that included back-to-back, two-run hits from Pedro Florimon and Aaron Hicks.
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