On February 3, 2016, Lee signed a minor league contract with the Seattle Mariners of Major League Baseball. The Mariners added Lee to the 40-man roster on March 27, 2016.
On April 8, 2016, Lee recorded his first career major league hit, a home run off of Eric Surkamp in a game against the Oakland Athletics. On April 13, 2016, Lee hit a pinch hit walk off home run to beat the Texas Rangers. This was the first rookie pinch hit walk off in Mariners history. On May 4, 2016, Lee hit two home runs in a 9–8 victory over the Oakland Athletics.
On June 10, 2016, Lee recorded back-to-back home runs off of Derek Holland, totaling 4 RBI to propel the Mariners to a 7–5 victory over the Texas Rangers.