The homer was No. 493 for Ortiz, tying him with Hall of Famer Lou Gehrig and Fred McGriff for 27th on the all-time list.
"What impresses me about David is he's never seen the guy," said Red Sox interim manager Torey Lovullo. "First-pitch fastball and he hits it over the left-center field wall for a home run. Nothing he does surprises me anymore, that's for darn sure. It got us going. It got us pushed in the right direction and it gave us a kick-start."
Ortiz, who started at first base, had to leave the game in the bottom of the eighth with tightness in his left heel. The injury isn't believed to be serious.
Ian Browne is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.