Ortiz and the Red Sox will try to close out their four-game series against the Astros on Sunday by snapping Collin McHugh's string of impressive outings.
Houston (51-73) was 0-8 all-time in Boston before a 5-3 win Friday and appeared ready to claim another victory the next night after taking a 6-3 lead into the fifth inning.
The Red Sox, though, rallied for a 10-7 win and Ortiz had four of his career high-tying six RBIs during that comeback. After hitting his 400th home run with Boston in the third inning, he had another two-run shot in the fifth and a two-run double in the eighth.
Ted Williams (521) and Carl Yastrzemski (452) are the only other players to hit 400 homers with the Red Sox.
"He's the main cog in the lineup. Whether there's been different guys in the lineup, it hasn't affected the overall power and production," manager John Farrell said after his club's seventh win in 10 games and just its third in the last nine home contests. "He's having one heck of a year once again."
The Red Sox (56-66) would likely have trouble repeating Saturday's hitting performance if McHugh (5-9, 3.08 ERA) can stay in his groove.
The Houston right-hander has allowed one run in each of his first three starts this month, totaling 19 1-3 innings, but he didn't break a nine-game winless stretch until Tuesday's 10-4 victory over Minnesota.
McHugh yielded four hits in six innings and walked none for the second straight outing while ending a string of six losing decisions.
"I've had a lot of losing streaks in my life. I was 0-8 to start my career, so it's nothing new and it's not something you consciously think about as a pitcher," he said. "You want to go out and throw zeros up in as many innings as you can and as long as you can."
McHugh is 2-3 with a 1.86 ERA in eight road starts this season as he heads into his first career matchup with Boston.
The Red Sox's Joe Kelly (0-0, 2.08) will make his first start against Houston, his first at Fenway and his first versus an AL team since being acquired from St. Louis on July 31. He gave up one run in seven innings to his former club in a 2-1 win Aug. 6 and allowed two runs in six innings in a 3-2 victory over Cincinnati on Tuesday.
Dexter Fowler is one of two Astros players to have faced Kelly, going 0 for 2 with a strikeout. McHugh is the other, and he grounded out in his lone at-bat versus the right-hander in a 5-4 loss for the New York Mets in St. Louis on Sept. 3, 2012.
Kelly hit one of his four career doubles off McHugh in that game.
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