His three-run blast in the seventh inning was the 6,106th home run of 2019, surpassing the record of 6,105 set in 2017.
These are the only two seasons in MLB history with at least 6,000 homers hit.
The previous record was 5,693 set in 2000.
Villar's 21st homer of the season gave the Orioles a 5-2 lead on the way to a 7-3 victory.
While there had been no doubt for some time that the record would fall in this homer-happy season, there was a touch of irony in the milestone dinger being hit by an Oriole, since Baltimore have shattered the record for home runs allowed in a season.
They had surrendered 279 coming into the game and gave up another to the Dodgers.
But with the win secured and the record set, the Orioles and Villar weren't quibbling.
"It's unbelievable," said Villar, whose bat was collected to be taken to the Baseball Hall of Fame. "I'm not going to be able to sleep tonight."
With 18 days remaining in the regular season, the record will be extended.
Across MLB there have been 1,000 or more home runs in each complete calendar month this season.
May's 1,136 home runs across the majors was a record for a calendar month, which was broken by June's 1,142 and August's 1,228.