Cleveland’s Jose Ramirez gestures while running to first after hitting his third home run of the night in the sixth inning Thursday against the Red Sox. Sue Ogrocki/Associated Press

CLEVELAND — José Ramírez homered in his first three at-bats — and from both sides of the plate — to power the Cleveland Guardians to a 10-3 victory over the Boston Red Sox on Thursday night.

Ramírez connected for a solo shot in the first inning off Matt Dermody (0-1), belted a two-run shot – his 200th career homer – in the third and added another solo blast in the sixth when the Guardians had eight straight hits and scored five times.

Ramírez came up a second time in the sixth bidding for a rare four-homer game, but struck out swinging. The four-time All-Star third baseman had another chance in the eighth, but grounded to third.

There have only been 16 four-homer games in the majors since 1901. The last to do it was Arizona’s J.D. Martinez in 2017. Cleveland got one from Rocky Colavito on June 10, 1959.

Ramírez also showed off some of his defensive prowess in the sixth by backhanding Justin Turner’s hard shot and throwing off balance across the diamond to get Boston’s third baseman while backpedaling in foul territory.

Will Brennan added a homer as the Guardians won the series and handed the Red Sox their fifth loss in six games.

Aaron Civale (2-1) had his second solid outing for Cleveland after spending 46 games on the injured list with an oblique strain. The right-hander pitched five scoreless innings last week at Minnesota, and kept the Red Sox off the scoreboard until the fifth, when Reese McGuire hit a two-out RBI double.

Triston Casas chased Civale in the sixth with his seventh homer to pull Boston within 3-2.

But Cleveland, whose offense has awakened after a slow start, pounded former teammate Corey Kluber in the sixth. After Ramírez homered, Andrés Giménez hit a two-run double, Myles Straw hit an RBI triple and Brennan singled home a run as the Guardians opened an 8-2 lead.

Kluber, who was recently demoted to the bullpen, was tagged for seven runs and 11 hits in 3 1/3 innings.

Dermody’s first major league start came with some controversy. The left-hander posted a homophobic tweet in 2021, and since deleted it, that the Red Sox were not aware of when they signed Dermody in January. He participated in the team’s mandatory anti-discrimination and harassment prevention training in March.

The team called Dermodys’ post “hurtful” and Manager Alex Cora praised the club’s handling of the matter.

NOTES: Red Sox outfielder Alex Verdugo was not in the starting lineup after being benched for not hustling in Wednesday’s loss. With Boston trailing 5-2 in the seventh inning, Verdugo slowed up between first and second base on a ball hit by Masataka Yoshida. Cora felt like Verdugo should have been running harder and immediately pulled him. “We just felt like on that play his reaction wasn’t a great one, not hustling his behind to second,” Cora said. “I don’t know if he was out or safe, but I didn’t like it. … I felt like it wasn’t acceptable, and he knows it.” … Red Sox infielder Yu Chang (left hamate fracture) will continue his rehab assignment at Triple-A Worcester this weekend and rejoin Boston’s roster on Monday. … LHP Richard Bleier (shoulder inflammation) is not recovering as quickly as the team expected. He recently began playing catch for the first time since going on the IL on May 22.