Cleveland captured the winner-take-all showdown to seal the American League division series 3-2 and reached a best-of-seven AL Championship Series (ALCS) match-up with the New York Yankees that starts on Monday in New York.
The AL champion will face the National League champion, the New York Mets or Los Angeles Dodgers, in the World Series.
Cleveland, into the ALCS for the first time since 2016, has not captured the MLB crown since 1948 and has not reached the World Series since 2016.
Thomas blasted his bases-loaded home run in the fifth inning and drove in another run in the seventh to power the Guardians.
"It's incredible," Thomas said. "You just love coming through for your teammates in that situation. Our bullpen has been grinding this whole series and to make all those innings worth it, it feels awesome."
Cleveland used eight pitchers to frustrate Detroit batters, combining to strike out 16 while scattering seven hits and six walks as closer Emmanuel Clase retired the last six Tiger batters over the final two innings.
"Watching him all year has been incredible," Thomas said of Clase. "It was cool to see him get those last outs."
Detroit's left-handed pitcher Tarik Skubal - the game-two winner who led the AL this year with 18 wins, 228 strikeouts and a 2.39 earned-run average - struck out six over six innings but surrendered the pivotal grand slam to Thomas.
"He threw me a good pitch to hit," Thomas said of the grand slam offering. "He threw one pitch over the middle and I happened to put a good swing on it, simple as that.
"It was good to come through."
The Tigers escaped a bases-loaded jam in the third inning when Thomas popped out to first base.
The game was scoreless until the fifth, when Detroit's Trey Sweeney walked and scored on Kerry Carpenter's single off the right-field wall.
'It only takes one'
The Guardians loaded the bases again in their half of the fifth on singles by Andres Gimenez, Steven Kwan and David Fry and then Skubal hit Jose Ramirez in the left forearm to force in the tying run.
It was the first run allowed by Skubal after 28 2/3 scoreless innings since September 18.
Thomas then followed with his bases-clearing grand slam to give Cleveland a 5-1 advantage.
"I don't know how many scoreless innings he threw," Thomas said. "But it only takes one (pitch)."
Detroit answered in the sixth when Spencer Torkelson doubled, took third on a wild pitch by Tim Herrin and scored on a Jake Rogers single, but the Tigers left the bases loaded when Carpenter struck out.
The Tigers, who last won the World Series in 1984, pulled within 5-3 in the seventh when Riley Greene singled and scored on a double by Colt Keith.
Cleveland responded in the seventh when Kwan singled, took third on a Ramirez single and scored when Thomas singled for a 6-3 advantage.
The Guardians added another insurance run in the eighth when Gimenez doubled and scored on Brayan Rocchio's single.
Clase entered for the Guardians in the eighth and the 26-year-old Dominican right-hander sent down the Tigers' final batters in order for the victory.
