Gilgeous-Alexander, the reigning NBA and NBA Finals Most Valuable Player, drew a crucial foul with 2.3 seconds remaining before nailing two free throws to settle an epic duel with a new-look Rockets side spearheaded by Kevin Durant and Alperen Sengun.
Gilgeous-Alexander's winning free throws settled a triumphant occasion for Oklahoma City, who had earlier been presented with diamond-encrusted championship rings to mark last season's NBA Finals victory.
However, after watching Oklahoma City hoist the franchise's first-ever championship banner, the Rockets had threatened to spoil the party for long periods with Sengun and Durant combining superbly to keep Houston in front for much of the game.
"Grit, determination, and defense," Gilgeous-Alexander said when asked to sum up the Thunder's nail-biting win.
"We know that when we do it (on defense), we give ourselves a chance no matter what's going on - makes, misses, good luck or bad luck. We did enough defense tonight to get the win. We're pretty rusty, but it's a good start."
Gilgeous-Alexander was backed by 28 points from Chet Holmgren, while Ajay Mitchell caught the eye with 16 points off the bench, including three three-pointers.
Turkish star Sengun led the Houston scoring with 39 points, including five three-pointers, while Durant, who joined from the Phoenix Suns in the offseason, added 23 points.
The Rockets had led by 12 points in the third quarter, but Oklahoma City came roaring back to edge ahead late in the fourth quarter.
Durant put the Rockets back in front 104-102, but Gilgeous-Alexander's pull-up with three seconds remaining knotted the score once more and took it to overtime.
The back-and-forth nature of the contest - which saw no fewer than 22 lead changes - continued in overtime before Gilgeous-Alexander cleverly drew what turned out to be the decisive foul from Durant to secure the pair of free throws that settled the game.
Gilgeous-Alexander had earlier been front and center of the festivities as Oklahoma City's players were presented with their championship rings to mark last season's title.
"On behalf of the organization, myself and my teammates, we just want to say thank you," Gilgeous-Alexander said in remarks to the home crowd.
"From the moment we stepped here, the love has been unconditional. Whether we were losing by 40 or winning by 40, you guys never wavered and we will never forget that."
"This ring is just as much ours as it is yours."