From rookie Gunnar Henderson recording three hits and scoring three runs atop the order to Ryan O'Hearn finishing 5-for-5 for his first career five-hit game, the Orioles (94-56) were bolstered by contributions up and down their order.
They will hope for similar performances on Tuesday when the teams play the middle contest of a three-game series.
Cedric Mullins, who went 2-for-5 with four RBIs, struck the decisive blow with his three-run home run in the ninth inning off Astros closer Ryan Pressly. It was part of another collective effort for Baltimore, which extended its lead in the American League East to 2 1/2 games over the idle Tampa Bay Rays (92-59).
The Orioles trailed 7-5 heading to the ninth inning.
"We just kept fighting, honestly," Orioles manager Brandon Hyde said. "Things were not going our way. It felt like it was, then it wasn't. For our hitters to answer the bell there and continue to score runs and continue to keep us in the game and pick people up, that was massive."
Right-hander Kyle Gibson (14-9, 4.98 ERA) has the starting assignment for the Orioles on Tuesday.
He took a loss in his latest outing, on Wednesday against the St. Louis Cardinals, after surrendering one run on three hits and three walks with four strikeouts over 6 2/3 innings. Gibson threw a season-high-tying 104 pitches in his 16th quality start of the season and 11th outing in which he gave up two earned runs or fewer.
Gibson is 4-3 with a 2.45 ERA over 13 career starts against the Astros, though he hasn't faced them since 2021.
Rookie Hunter Brown (11-11, 4.61) is the scheduled starter for Houston on Tuesday.
The right-hander twirled five hitless innings against the Oakland Athletics on Wednesday, issuing two walks while recording seven strikeouts in a 6-2 win. Brown had gone 4-8 with a 6.41 ERA in his previous 14 appearances (13 starts).
Brown is 0-1 with a 6.43 ERA over two career appearances against the Orioles. His lone start against Baltimore came on Aug. 10, when he allowed five runs on eight hits with seven strikeouts and no walks over six innings in a 5-4 road loss.
The Astros (84-67) saw their AL West lead over the Texas Rangers and Seattle Mariners, both 82-68, slip to 1 1/2 games as they lost for the fifth time in seven games. The Astros rallied from a two-run deficit only to blow a pair of two-run leads, the second with Pressly on the mound in the ninth.
Pressly posted eight consecutive scoreless outings before surrendering four runs and blowing a save chance against the Detroit Tigers on Aug. 25. He was unable to complete a combined no-hitter on Wednesday when he allowed two runs on two hits and one walk against the Oakland Athletics.
The collapse on Monday amounted to a gut punch at the end of a seesaw game.
"It was devastating, but you've got to get over it," Astros manager Dusty Baker said. "You can't bring it back. That hurt a lot.
"Yeah, that was a tough loss."
—Field Level Media