Plouffe cleared waivers and has elected to become a free agent.
The 30-year-old was a first-round draft pick of the Twins back in 2004. After struggling to earn a spot as a shortstop, he turned himself into a reliable third baseman with solid power.
Plouffe hit .247 with 96 home runs and 357 RBI in seven seasons with the Twins. The move appears to open a spot at third base for young slugger Miguel Sano, who bounced around between designated hitter, third base and the outfield last year.
Third base has always been Sano's preferred position.
Plouffe was limited to 84 games last season because of injuries. He batted .260 with 12 homers and 47 RBI.
The Twins also outrighted catcher Juan Centeno off the 40-man roster Friday.
The team says outfielder Adam Brett Walker has been claimed off waivers by the Milwaukee Brewers.