The Red Sox's designated hitter is the 19th active player to reach the 300-homer plateau. Ortiz, who joined the Sox in 2003, has gone deep 10 times in his past 29 games following a two-month slump to open the season.
"There was a lot of frustration at the beginning of the year," Ortiz said. "I was trying to do things, and nothing was happening. Right now I'm just trying to relax and let things happen."
Ortiz made something happen in his first at-bat on Thursday, swinging his way into the history books.
"When the ball's coming off his bat like that, that's good for us," manager Terry Francona said. "He's back to being about as dangerous as anybody in the league."
The milestone was somewhat bittersweet for the gregarious slugger, as Thursday marked the first time this season the Red Sox did not win a game in which he homered. By losing the opener, Boston fell into a first-place tie with the Yankees in the American League East.
"Three hundred home runs is definitely something you want to get done in your career," said Ortiz, who has reached double digits in homers in each of the past 10 seasons. "It means a lot. But the main thing is, you want to hit it when your team is winning, you know?"
The 33-year-old, who is now one hit shy of his 1,000th knock since arriving in Boston, is the first player to hit his 300th home run in a Red Sox uniform since Manny Ramirez achieved the feat on Aug. 26, 2002.
John Barone is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.