One of the NBA's most potent attacking sides, the Thunder began Monday's (AEDT) road game with an 11-2 run and never again trailed, finishing up 134-91 winners.
Only twice since the turn of the century have the Thunder, or predecessors the Seattle Supersonics, scored bigger victories - both were by 45 points in 2012 and 2013.
The latest win would have equalled those 45-point margins if not for a dunk from Portland's Moses Brown in the final 30 seconds.
Victory came despite Oklahoma City coach Mark Daigneault beginning to send his starting five to the bench with five minutes to play in the third quarter. None returned after the final change.
Six Thunder players scored in double figures, with Shai Gilgeous-Alexander leading the way on 28.
Australian guard Giddey had a team-high five assists to go with six points and four rebounds.
The Thunder shot at 71.8 per cent from the field before half-time, the most accurate first-half shooting display from any side this season.
They parlayed their precision into a 33-point half-time lead, all but sealing victory with two quarters to play.
"Our execution of the game-plan really set the tone for the game and got us a nice grip on the game early," Daigneault said.
"That was a by-product of maturity and discipline."
The loss was Portland's seventh in a row as life without Milwaukee recruit Damian Lillard continues to weigh on the Blazers.
Australians Reath and Thybulle combined for only six points from the bench.
After Houston's Alperen Sengun tied the game at in the final five seconds, 38-year-old James was fouled driving to the basket at the other end.
The 21-year NBA veteran stepped to the charity stripe to win the game but missed his first attempt.
His second sailed into the hoop to improve his tally to 37 points from 73.7 per cent field-goal shooting. He finished with a team-high eight assists.
With one last chance to seal victory, Dillon Brooks' long-range three-point attempt deflected from the backboard and the Lakers held on for their fifth win in six games.
Utah's Lauri Markkanen (38 points, 17 rebuonds) booked overtime with a lay-up that tied the game at 115 in the final 20 seconds.
An 11th-hour dunk from Kristaps Porzingis helped Boston survive a scare from Memphis and run out 102-100 winners on the road.
Memphis missed two shots that could have helped snatch the game back and had another blocked, slipping to 3-10 for the season as the Celtics pieced together a six-game winning streak.