Mauer drove in three runs and Michael Cuddyer added a three-run homer for the Twins.
Francisco Liriano (2-4) allowed six hits and five runs over five innings for the victory.
Seattle starter Felix Hernandez (4-2) gave up six runs on six hits in four innings to take the loss.
Adrian Beltre had three hits, including a homer, and two RBI for the Mariners. Mike Sweeney added a two-run homer and Ichiro Suzuki had two hits and scored two runs for Seattle, which has lost six straight.