Thome did that Saturday, doubling in the go-ahead run in a 9-6 win in 12 innings over the Boston Red Sox that was Baltimore's 16th straight victory in games that reach overtime.
The 22-year veteran came through in his first game after nearly two months on the disabled list, enabling the Orioles to remain one game behind the first-place New York Yankees in the AL East. They lead the Oakland Athletics by two games for the league's No. 1 wild-card berth.
"This situation is not new to him," said Adam Jones, who doubled and scored on Thome's hit. "He's missed some time, but stepping into that box ... he always rises to the occasion."
Just as the Orioles rise to the challenge of extra-inning games. Their winning streak in those games is the best in the majors since the Cleveland Indians won 17 straight in 1949. The Orioles are 16-2 in extras this year, losing only to the Yankees on April 10-11.
"We've had so much experience at it, there's not some sense of panic," Baltimore manager Buck Showalter said.
The Orioles won their sixth in a row overall.
Thome had two homers, six RBIs and 10 walks in 18 games after being acquired from Philadelphia on July 1 before going on the disabled list from July 31 until Friday with a herniated disc in his neck.
"These guys have been playing very well and to come in and get a big hit like that is big," he said. "You want to be a part of what they're doing and I think that's what makes you work hard when you're down (in the minors) because you really don't know when you're on rehab how the process is going to go. So being here and being in this atmosphere, you enjoy every minute of it."
Thome was having a rough day in his first appearance since July 27, and was 0 for 5 with a double play and two strikeouts. But the slugger gave Baltimore a 7-6 lead with his ground-rule double off Alfredo Aceves (2-10). Endy Chavez and Manny Machado added RBI singles to pad the lead.
"The game is a weird game. That's what makes it so fun," Thome said. "You can be 0 for 5 and continue to be positive and keep battling and you get a big hit like that."
Jones earlier hit his 31st home run.
The Red Sox are 0-7 in extra-inning games at home.
"At the end of the season, the teams that you see go into the playoffs pull out the extra-inning games," Boston's Cody Ross said. "We just haven't been able to do that this year."
Their lineup Saturday had seven players, including starter Aaron Cook, who spent time in the minors this year.
"When you don't have the firepower for the big hit," Boston manager Bobby Valentine said, "the guys came up short."
Trailing 6-3, the Red Sox tied the game with two runs in the seventh and one in the eighth.
In the seventh, they loaded the bases with no outs against Jake Arrieta on a double by Scott Podsednik, a walk to Pedro Ciriaco and an infield single by Dustin Pedroia. Ross and Ryan Lavarnway each drove in a run when they grounded into forceouts.
The Orioles took a 1-0 lead in the first when Nate McLouth led off with a walk, stole second, moved up on a groundout and scored on a grounder by Jones. The Red Sox tied it in the bottom half on a ground-rule double by Pedroia and a single by Lavarnway.
Baltimore made it 2-1 in the second on an RBI single by Machado then added a run in the fourth on a leadoff homer by Mark Reynolds, his 22nd of the year.
Boston tied it in the bottom half of the fourth on a leadoff single by Mike Aviles and Danny Valencia's first homer since the Red Sox acquired him from the Minnesota Twins on Aug. 5. It was his third of the season.
The Orioles went back on top 5-3 in the sixth on a two-run triple by Ryan Flaherty, starting for second baseman Robert Andino, who was in uniform but didn't play after being hit on the left ear flap of his helmet by a pitch in the ninth inning of Baltimore's 4-2 win on Friday night. Results of a CAT scan were negative and Showalter said that, pending results of other tests, he might play Sunday.
Jones made it 6-3 in the seventh with his homer.
"I'm tired of playing extra-inning games, to be honest with you," Jones said, "but, hey, we're not quitting 'til that last out is made, and if we need 13, 14 15, up to 18 innings to do the job, then I guess that's just what we have to do."
Three of the Orioles last four games have gone extra innings, wins at Seattle of 4-2 in 18 innings and 3-1 in 11 before opening the series in Boston. .... The three Red Sox in the lineup who haven't been in the minors this year were Aviles, Pedroia and Ross. ... Cook had won his previous start after going 0-5 in six before that. ... Cook had allowed just one stolen base, the fewest among AL pitchers with at least 80 innings, before McLouth stole second in the first. ... Chris Tillman (8-2) pitches for Baltimore against Felix Doubront (11-9) in Sunday's finale of the three-game series.