Hargrove was to manage Sunday's game against Toronto and will be succeeded by John McLaren, his bench coach. McLaren's first game as manager will be Monday against Kansas City.
The Mariners have won seven straight games, and Hargrove's startling resignation came hours before the team tried to extend its longest winning streak in more than four years.
"Over the past several weeks, I have come to the realization that to be fair to myself and the team, I cannot continue to do this job if my passion has begun to fade," the 57-year-old Hargrove said in a statement.
Hargrove was in the middle of his 16th season. He led Cleveland to two World Series, in 1995 and '97. He had six consecutive losing seasons in Baltimore and Seattle before the Mariners' surprising surge this year. Seattle was four games behind the Los Angeles Angels in the AL West entering Sunday.
"I am very proud of the work we've done to turn this club around in three years, and I have high expectations for the team this season," Hargrove said.