Carlos Correa and Gio Urshela added RBIs for the Twins, whose lead in the American League Central remains one game over Cleveland.
Entering to a nice ovation, Lopez, an All-Star acquired Tuesday from Baltimore, earned his 20th save of the season with a 1-2-3 ninth inning.
''It's a time where to just even think about being here, being in that spot, to be in first, it's just fun. Really fun to watch these guys daily. I love it,'' Lopez said.
He needed just seven pitches, including a three-pitch strikeout of Eric Haase.
''I love to go out there, be quick. If it's not, we battle,'' Lopez said.
Lopez's outing came after Minnesota starter Joe Ryan bounced back from a career-worst outing with five mostly solid innings. Michael Fulmer then pitched a scoreless inning in his Twins debut against the team from which he was traded Tuesday, before Caleb Thielbar and Jhoan Duran each tossed a scoreless frame.
''We saw some guys with some electric stuff. They made good pitches. They threw the ball the way they wanted to,'' Twins manager Rocco Baldelli said. ''We saw some elite sliders from Fulmer. We saw Lopez go out and have as dominant and clean of an inning as you want to see. It's exciting to turn the ball over to those guys, let them do their thing out there. But that's really good looking stuff from our bullpen and Joe Ryan.''
Rocked on Saturday in San Diego, allowing 10 earned runs and five home runs in 4 2/3 innings, Ryan (8-4) tied a season high with nine strikeouts - also April 27 vs. Detroit - and allowed three hits as he again dominated the Tigers. In three 2022 starts against Detroit, Ryan is 3-0 with a 1.02 ERA and 25 strikeouts in 17 2/3 innings.
He hit two batters in the fifth before Riley Greene's RBI single.
''Didn't really have a good feel for my changeup, which was working last time, so I think they were probably sitting on that a little more because it worked so well last time. Just getting after it, attacking hitters,'' Ryan said.
Acquired Tuesday from Cleveland, Leon had two hits, including a two-run double in the second for Minnesota. He had two hits in 15 at-bats for the Guardians this season, spending much of the year in the minors.
A Correa line drive in the sixth nearly hit Byron Buxton near second base but got through as the speedy Buxton raced home.
Harold Castro had three of Detroit's four hits.
Detroit struck out 14 times Wednesday, 41 times in the three-game series, and has whiffed 148 times in 17 games against Minnesota this season.
''He beat us, Joe Ryan did today, with fastballs in the zone. It's one thing when you chase, it's another when you get beat in the zone,'' said manager A.J. Hinch. ''... When you swing and miss like that, it's hard to produce offensively. ''
Making his second straight start after two months in the bullpen, Tyler Alexander (2-5) was the hard-luck loser, allowing two hits and striking out five in five innings. He retired the Twins in order in four of those frames.
UNDER THE SUN
Detroit has played 53-day games, the most in baseball, and 52 night games. This was Minnesota's 48th day game, tied with the White Sox for fourth most in the majors. Cleveland has played 51 and Oakland 50.
Both teams made a quartet of moves before the game. Minnesota made another after.
Detroit placed LHP Tarik Skubal (left arm fatigue) on the 15-day injured list retroactive to Tuesday, and reinstated RHP Wily Peralta (strained left hamstring) from the IL. The Tigers also optioned IF Zack Short to Triple-A Toledo and recalled OF Daz Cameron from the Mud Hens.
For Minnesota, Thielbar (left hamstring strain) was reinstated from the 15-day IL. The contract of Leon was selected from Triple-A St. Paul. RHP Joe Smith was designated for assignment and C Caleb Hamilton was optioned to St. Paul.
LHP Jovani Moran will be optioned to St. Paul to make room for starter Tyler Mahle, acquired Tuesday from Cincinnati. Mahle is to be activated tomorrow.
Tigers: In a 0-for-19 skid, DH Miguel Cabrera did not play. Hinch said Cabrera's right knee is bothersome, and he plans to give the 39-year-old a few more scheduled days off the rest of the season.
Twins: Buxton went 1 for 3 as the team's DH after sitting the past two days with a sore right knee that was thoroughly evaluated Tuesday by trainers.
Tigers: Welcome Tampa Bay on Thursday for the first of four games. Detroit's Drew Hutchison (1-4, 4.53) is scheduled to oppose Rays LHP Jeffrey Springs (3-3, 2.70).
Twins: RHP Sonny Gray (6-3, 3.41) is to pitch Thursday when Minnesota starts a four-game home series with Toronto. Alek Manoah (11-5, 2.43) is the Blue Jays scheduled starter.
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