The Astros haven't been to Boston since 2003, when they were swept in a three-game series, the first ever played between the two clubs.
Now bumping shoulders in the American League, the Astros (7-14) are set to begin a new rivalry with the Red Sox (14-7), who after a 6-5 win over the A's on Wednesday share the best record in the AL with the Rangers.
Philip Humber will take the mound for Thursday's game, set to begin at 6:35 ET.
"It's a fun place to play for me," said Humber, who is 2-0 in two career starts at Fenway Park. "I think it's the coolest stadium in the Major Leagues as far as the ones I've been to. It's got that old feel, but at the same time, they've done a lot of things to update it."
Humber is coming off perhaps the worst start by any pitcher this season, when he retired just one batter before being removed against the Indians last Saturday. The 30-year-old righty allowed eight runs on eight hits and a walk.
Humber will be charged with containing a Red Sox offense that entered Wednesday ranked third in the AL with 94 runs scored and includes Mike Napoli, who leads the Majors with 26 RBIs, and David Ortiz, who had a hit in each of his first four games since returning from the 15-day disabled list Saturday.
Carlos Pena, who grew up in Haverhill, Mass., and was a standout at Northeastern University, makes his return to Fenway, where he's a career .248 hitter with an .815 OPS and 11 home runs in 218 at-bats.
"It's going to be awesome," said Pena, who has two homers this season. "Everybody's going to enjoy it. There's so much history there. It's a special place."
Unfortunately for the Astros, their American League debut at Fenway will come against one of the game's hottest pitchers in Clay Buchholz, who is out to a 4-0 start.
Buchholz has sparkled in four starts, striking out 29 batters while opponents are hitting just .184 off him. He leads all qualified starters in the Majors with a 0.90 ERA.
Astros: Barnes filling in for Maxwell
The Astros placed Justin Maxwell on the 15-day disabled list after he fractured his left hand while being hit by a pitch in the third inning Tuesday. Robbie Grossman was called up and started in center field against left-hander Joe Saunders on Wednesday, though Brandon Barnes is expected to get much of the playing time in Maxwell's absence.
"He's been outstanding -- defense, big hits," Astros manager Bo Porter said of Maxwell. "We'll need other guys to step up."
Barnes is hitting .367 with a home run and two stolen bases this season. The 26-year-old excelled in the Minors last season, hitting .321 with a .381 on-base percentage, 12 homers and 21 steals in 399 at-bats between Double-A Corpus Christi and Triple-A Oklahoma City.
Red Sox: A familiar face
The Red Sox recalled reliever Daniel Bard from Double-A Portland on Wednesday. Bard had thrown nine innings with Portland, striking out four while walking four and posting a 4.00 ERA.
Bard is not expected to pitch in late-game situations just yet.
"Right now, I think it's a matter of him getting back, acclimated to this level and building some confidence along the way," manager John Farrell said. "[His fastball] is not back to the upper 90s. That doesn't mean he has to get back to that level to be successful. It's been 93-96 range. I think a lot of guys would sign up to be able to throw that hard."
• On Wednesday, Brandon Laird hit his second home run since being called up from Triple-A Oklahoma City on Thursday. The right-handed-hitting first baseman had a .353 average and .932 OPS in 12 games before his promotion.
• The Red Sox invited fans who purchased tickets for Tuesday's rain-shortened game against the A's to bring their tickets back and exchange them for admission into Thursday night's game against the Astros.
• Red Sox pitchers lead the Majors with 207 strikeouts. They've fanned at least 10 batters in a game 13 times this season.