Sano extended his home run streak to four consecutive games for the first time in his career. He has hit eight of his 11 homers since May 11.
"I felt pretty good," said Mauer, who was 5-for-12 in the series with two walks. "The last three days I felt like I was really driving the ball, using my legs, and I was glad to see a couple go out."
The Twins trailed, 2-1, when Mauer opened the fourth inning with his seventh home run, an opposite-field shot to left off Mariners starter Taijuan Walker.
"This series, Seattle was really working me away," Mauer said.