HOUSTON -- Justin Verlander pitched a two-hitter and lost, allowing homers to John Hicks and Ronny Rodriguez, and the Detroit Tigers beat the Houston Astros 2-1 on Wednesday night in a historic upset.

With Verlander on the mound at home against the team with the majors' worst record, the Tigers (38-86) closed as +435 underdogs at Caesars Sportsbook, making their win against the Astros (81-47) the largest upset in a major league game in the past 15 seasons, according to ESPN Stats & Information research.

Caesars also saw the Astros close as -560 favorites, making them the heaviest favorite in a game in at least the past 15 seasons, according to sports betting database BetLabsSports.com, and likely longer.

Roxy Roxborough, a longtime oddsmaker and bettor, told the Las Vegas Review-Journal last week that he remembered a few -500 favorites in years past involving pitchers such as Nolan Ryan, Randy Johnson and Pedro Martinez, but not many.

Clayton Kershaw and the Los Angeles Dodgers were -485 favorites over the Atlanta Braves in 2016, and earlier this month, the Astros were -460 road favorites over the Baltimore Orioles. Houston lost that game 8-7 in what was, before Wednesday, the largest upset since the Washington Nationals beat the Minnesota Twins as +395 underdogs in 2007.

Verlander (15-5) retired the first 14 batters Wednesday night, with six strikeouts, before Rodriguez homered to the seats in right with two outs in the fifth. Verlander sat down another 10 straight before Hicks led off the ninth with a tiebreaking blast to left-center field.

Verlander, who spent 13 seasons with the Tigers, walked none and finished with 11 strikeouts in his 99-pitch gem, extending his franchise record of games with 10 or more strikeouts to seven as he lost for the first time since June 18.

He leads the majors in strikeouts with 239 but ranks second in homers allowed with 33.

Robinson Chirinos belted his 14th homer, to left-center, on Tyler Alexander's first pitch of the seventh to tie it at 1. Chirinos finished with four hits. Needing a triple for the cycle, he doubled with two out in the ninth but was thrown out trying to reach third to end the game.

Opener Daniel Norris allowed two hits in three innings for Detroit. Alexander worked four innings, Buck Farmer (5-4) walked one in a scoreless eighth and Joe Jimenez finished the Tigers' six-hitter for his fourth save.

Jose Altuve walked with one out in the eighth, but was erased when he tried to go first to third on an infield grounder by Alex Bregman to end the inning.

TRAINER'S ROOM

Astros: RHP Josh James (shoulder soreness) will begin a rehabilitation assignment with Triple-A Round Rock on Thursday night. Manager AJ Hinch said James, who has been out since July 23, likely won't rejoin the team until September. ... INF Aledmys Diaz took batting practice Wednesday and could come off the injured list early next week. Diaz was hospitalized Saturday after experiencing dizziness on the team bus in Oakland, California.

UP NEXT

Tigers: RHP Jordan Zimmermann (1-8, 6.66 ERA) is scheduled to start for Detroit when the series wraps up Thursday night. Zimmerman allowed just one hit in five scoreless innings in his previous start, against Tampa Bay, but did not factor in the decision.

Astros: RHP Gerrit Cole (14-5, 2.87) will start Thursday after being scratched from his previous start, last Thursday, because of discomfort in his right hamstring. Cole, who ranks second in the majors with 226 strikeouts, has won his past 10 decisions.

ESPN's David Purdum and The Associated Press contributed to this report.