Cruz hit a solo drive in the first, a two-run shot in the third and another two-run homer in the fifth. It's the first career three-homer game for the six-time All-Star, who has 385 home runs in his career.
Cruz batted again with a runner on first in the sixth and struck out swinging against Jimmy Cordero, ending the inning. He flied out to right leading off the ninth, ending the day 3-for-5 with five RBIs.
"It's not easy," Cruz said. "To be able to hit three is a blessing.
"The most important thing is we won and the way [Jose] Berrios pitched. At the end of the day, it's pitching."
Cruz went deep against All-Star Lucas Giolito on different pitches -- fastball, curveball and changeup.
"He's a good hitter,'' Giolito said. "He was seeing me well.''
Cruz's outburst followed three-homer games by New York Mets second baseman Robinson Cano on Tuesday night and St. Louis Cardinals shortstop Paul DeJong on Wednesday. According to Elias Sports Bureau research, it's the first time in major league history there's been a three-homer game on three consecutive days.
The 39-year-old Cruz, who signed a $14.3 million, one-year contract with Minnesota in January, has six homers in his past four games and 25 overall this season. According to Stats LLC, he is the oldest player in major league history to hit six-plus homers in a four-game span, surpassing Barry Bonds, who hit seven in four games at age 36 in 2001.
Cruz also became the 10th player in big league history with a three-homer game after turning 39, according to Baseball Prospectus data, joining a list that includes Babe Ruth, Stan Musial, Reggie Jackson, Dave Winfield, Frank Thomas and Alex Rodriguez.
"You just assume he's done things like that,'' Twins manager Rocco Baldelli said. "Those kind of nights are pretty unique and special, and when you get a chance to see them live, we all kind of enjoy them and appreciate them.''
Cruz is the only player with multiple four-game homer streaks this season. He also hit a homer in four consecutive games June 5-9, according to ESPN Stats & Information research. He is the oldest player with a three-homer game since Rodriguez did it four years ago against the Twins.
At 39 years and 24 days old, Cruz is the second-oldest player in the modern era (since 1900) with seven homers in a six-game span. Graig Nettles was 40 years and 4 days old for the sixth game of his streak in August 1984.
Information from The Associated Press was used in this report.