Pujols' 522nd homer came on a 1-0, 98-mph fastball, after Ventura had struck out the first two hitters.
"Obviously, it's a great accomplishment, but it's disappointing we got swept by a great ballclub," said Pujols, who added a double and went 2-for-3. "It's an honor and a blessing to be in the same name category as those guys. But, at the same time, I've got to stay humble, and do my best to help my team win, and I wasn't able to do that today."
Next on the career list is Jimmie Foxx (534). Only Foxx, Pujols, Hank Aaron and Alex Rodriguez reached 2,500 hits, 500 homers and 1,500 runs by their age-34 seasons.
"I think every time Albert hits a home run, it just keeps putting into perspective how great he is," manager Mike Scioscia said. "You're playing with a living legend, and he still loves to play the game."
Earl Bloom is a contributor to MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.