Naylor also had a run-scoring double in the eighth and finished with eight RBI for the Guardians, who stunned Chicago by erasing an 8-2 deficit in the ninth aided by two White Sox errors.
Andrés Giménez led off the inning with a homer and then doubled home a run in the 10th as the Guardians snapped Chicago's six-game winning streak. They have won eight of 10 following a seven-game skid.
It was the first multi-homer game for the 5-foot-11, 250-pound Naylor, back from a horrific leg injury last season. The 2015 first-round draft pick (by the Marlins) from Canada is 10 for 17 with runners in scoring position this year.
“He looks really good in the batter’s box,” Cleveland manager Terry Francona said. “And when things happen, how much it means, he’s really emotional. But I get it. He missed playing baseball and being with his teammates.”
Naylor launched his first career slam off Liam Hendriks, handing the All-Star closer his first blown save since April 8.
The White Sox loaded the bases on three walks in the bottom of the ninth, but third baseman José Ramírez made a diving, backhand stop to save the game and Naylor stretched far at first base to field the one-hop throw for the final out of the inning.
Naylor’s go-ahead drive came off Ryan Burr and barely cleared the right-field fence.
A pumped-up Naylor pointed and pounded his chest as he gestured excitedly all the way around the bases. Once he returned to the dugout, he shouted and fired his helmet toward the rack.
“That was a legendary moment,” Guardians teammate Franmil Reyes said.
Burr (0-1) started the 11th in place of Reynaldo Lopez, who felt lower back tightness while warming up and left the game.
White Sox starter Michael Kopech allowed two hits through six innings, and Chicago got three-run homers from Gavin Sheets and AJ Pollock to build a big lead. But four errors, which tied a season high set April 20 in the first game of a doubleheader, came back to burn the White Sox.
“Brutal,” manager Tony La Russa said. “Had a chance to put it away. That’s just a brutal loss, to give up six runs like that and a couple chances to win offensively. It’s a tough loss. It’s as tough as you’re going to have.”
Sheets dropped a line drive to right field with two outs in the first that allowed the Guardians’ first run to score. Chicago shortstop Tim Anderson and third baseman Yoan Moncada committed costly errors in the ninth.
Kopech lowered his ERA to 0.93, and his six innings tied a career high set Aug. 26, 2018, at Detroit.
The game marked the return of Moncada and the White Sox debut of reliever Joe Kelly. Moncada hadn’t played this season because of a right oblique strain. Kelly, who was out due to a right biceps nerve injury, pitched a scoreless seventh.
PAUSE ON CUETO
White Sox RHP Johnny Cueto will make one more start at Triple-A Charlotte, general manager Rick Hahn said. RHP Vince Velasquez will start Wednesday’s series finale against the Guardians.
Guardians: RHP Enyel De Los Santos was promoted from Triple-A Columbus. LHP Konnor Pilkington was optioned to Columbus.
White Sox: LHP Aaron Bummer (right knee strain) was placed on the 15-day injured list, retroactive to May 7. INF Jake Burger was optioned to Triple-A Charlotte.
White Sox OF Andrew Vaughn (right hand bruise) is making progress but is unlikely be activated from the 10-day IL when he’s eligible Thursday, Hahn said. ... RHP Lance Lynn (right knee surgery) is more likely to return in early June.
Guardians: RHP Cal Quantrill (1-1, 3.54 ERA) will face the White Sox on Tuesday night. Quantrill allowed three runs over six innings last Wednesday in a 6-5 win over the Padres.
White Sox: RHP Lucas Giolito (1-1, 3.20) gave up three runs in 5 2/3 innings last Tuesday in a 4-3 win over the White Sox.
Fantasy baseball pitcher rankings, lineup advice for Sunday's MLB games
Everything you need to know to place your MLB bets and set your fantasy baseball lineups for Sunday, May 22.
Fantasy Baseball Forecaster for Week 7: May 23-29
Set your lineups for the week ahead in fantasy baseball with our forecaster preview, which features pitcher rankings, two-start pitchers, hitter ratings, schedule observations and more.
Fantasy baseball forecaster: Team hitting ratings
Stay ahead of the game and optimize your fantasy baseball hitters with our forecaster, which provides a rolling 10-day outlook of every team's hitting matchups as well as the potential for stolen bases.
Fantasy baseball forecaster: Pitcher projections for the next 10 days
Keep up to date on who is pitching -- and how well they're expected to do -- with our forecaster, which provides a rolling 10-day outlook of every team's probable starting pitchers with game score projections.
Goldschmidt leads Cardinals against the Pirates after 4-hit outing
St. Louis Cardinals (22-18, second in the NL Central) vs. Pittsburgh Pirates (16-23, third in the NL Central)
Mariners look to break 3-game road skid, play the Red Sox
Seattle Mariners (17-24, fourth in the AL West) vs. Boston Red Sox (18-22, fourth in the AL East)