His shot down the right-field line, which came against A's right-hander A.J. Griffin, tied the game at 1.
"It was in a big situation to tie the game," Ortiz said. "A lot of people were expecting that. It was just very exciting."
Few people could have expected it when the Minnesota Twins released Ortiz following the 2002 season, and anyone could have signed him. The Red Sox were the team that showed the initiative, and they've been reaping the benefits ever since.
"He was the guy that bounced around a little bit and then went to Boston and found a home -- it's an inspirational story," said A's outfielder Brandon Moss, who used to play with Ortiz in Boston. "You look at the career he ended up having, and this isn't his last year. He's just an amazing person, and he's fun to watch hit, whether you're playing with him or against him."
When Ortiz crossed home plate, he got a hug from Adrian Gonzalez, who was in the on-deck circle. Dustin Pedroia and Cody Ross were among the first players to greet him on the top step of the dugout.
"It was awesome," said Ross. "It seems like every pitch he's got that chance to do it. As soon as it went in the air, it was just a sigh of relief, for him especially to get that weight off his shoulders. I'm just so happy for him and proud."
When Ortiz stepped to the plate again in the sixth, the Athletics' public-address announcer informed the crowd that Ortiz had hit No. 400 in his previous at-bat. The crowd gave him a standing ovation.
"Yeah, that was pretty cool," Ortiz said. "You're playing on the road and you get something like that done on the road and people really appreciate it. It just tells you the way the game is going on these days. It was a nice appreciation."
Ortiz became the 49th Major Leaguer to reach the 400-homer plateau and is the 21st lefty to do it.
Big Papi, who is in his 10th season with the Red Sox, is one of eight active players to hit 400 home runs.
Ortiz has been one of the most beloved players in Red Sox history, thanks in large part to his clutch heroics en route to World Series championships in 2004 and '07, as well as his gregarious personality.
At the age of 36, Ortiz is having one of his best all-around seasons. The home run Wednesday was his 22nd of the season.
Ortiz is the first player to hit No. 400 in a Boston uniform since Manny Ramirez, who accomplished the feat in 2005.
One of the elite sluggers of the last decade, Ortiz is the only Major Leaguer with 20-plus homers in each of the last 11 seasons.
For Ortiz, it took the seventh and final game of the West Coast road trip to reach the milestone. He belted No. 399 at Fenway Park on June 27, the last game of the homestand.
"When I first got to the big leagues, I was just excited to be in the big leagues," Ortiz said. "But it's just consistency. You've got to work through it. I just tried to keep on working as hard as I can to continue producing."