The teams announced the swap on Friday. Seattle sent Ben Gamel and Minor League right-handed pitcher Noah Zavolas to Milwaukee in the trade.
Santana, 26, hit .265 with five home runs and 20 RBIs in 85 games last season for the Brewers. He hit .278 with 30 home runs and 85 RBIs in 151 games during the 2017 season. Santana is eligible for arbitration this offseason.
The five-year veteran made his Major League Baseball debut in 2014 with the Houston Astros. He joined the Brewers as part of a 2015 trade.
Gamel, 26, hit .272 with a home run and 19 RBIs in 101 games last season for the Mariner. He hit .275 with 11 home runs and 59 RBIs in 134 games during his 2017 campaign with Seattle.
Zavolas, 22, posted a 3.03 ERA and a 5-2 record with two saves in 19 appearances last season at the Advanced-A and Short-Season-A levels.