The home side were 10 points up at the start of the fourth before Russell Westbrook and Kevin Durant got the Thunder back on level terms with five minutes remaining, but a late surge from Derrick Rose secured the victory for Chicago, leaving them unbeaten at the United Center so far this season.
Chris Bosh ensured that the visitors made a bright start, but they struggled to pull away from the Wolves, before Dwyane Wade added a couple of shots in the final three minutes, leaving Minnesota without a win at home so far this season.
Just a point separated the two teams at the interval, but Jefferson and Kemba Walker led the charge in the third quarter, extending the gap to 24 points early in the fourth.
The home side started to run up the score in the second quarter, with Damian Lillard leading the scoring for the Blazers with 27, including seven three-pointers.
CJ McCollum and Lillard kept the points coming in the second half, with Portland outscoring their opponents 40-25 in the third quarter.
After a closely-fought first half, the visitors started to open up a lead in the third quarter, before Hayward, who has been struggling with his shooting at the start of the season, made a three-pointer and a string of free throws.
Results in full: Oklahoma City Thunder 98-104 Chicago Bulls, Miami Heat 96-84 Minnesota Timberwolves, Charlotte Hornets 108-94 Dallas Mavericks, Utah Jazz 96-84 Denver Nuggets, Memphis Grizzlies 96-115 Portland Trail Blazers