It was Scott's 16th career double-double and helped the Buffaloes capture their 19th straight nonconference home win, a streak that dates back to 2011.
Xavier Johnson, Askia Booker and Wesley Gordon all began on the bench in an unexpected move by coach Tad Boyle. The trio started nearly every game last season. It also marked the first time Booker hasn't started a game since the 2011-12 season.
Booker helped the Buffaloes gain some separation in a close game with a three-point play midway through the second half. At first, Booker was called for charging as he barreled into the lane and over Lee for a layup. But the officials switched it to a blocking foul on Lee, who picked up his fourth foul. Drexel coach Bruiser Flint was irate by the call reversal that ended up giving Colorado a 47-37 lead.
Before the game, Scott spent more than 30 minutes shooting jumpers over an assistant coach holding up foam fingers. Scott then went out and did the real thing against anyone Drexel assigned to guard him.
The 6-foot-10, 245-pound Scott even drained a late 3-pointer, drawing the loudest cheer of the night from the crowd.
It's the third time in Scott's career he's scored 21 points in a game.
Flint's mid-major squads have picked up quite a few impressive wins over his 14 seasons. His teams have knocked off teams currently in the ACC (Louisville), Big East (Villanova, Creighton), Big Ten (Rutgers), SEC (Alabama) and AAC (Temple).
But the Dragons couldn't add the Pac-12 to that list. Drexel is now 0-6 against the conference.
Colorado never trailed in the first half and led by as many as nine, but couldn't pull away from Drexel, which stayed close by making one long 3-pointer after another. The Buffs took a 33-29 lead into the locker room.
Drexel: It's the second straight season the Dragons began against a Pac-12 school, losing to UCLA by five points a year ago.
Colorado: CU improves to 61-9 at Coors Events Center under Boyle.
Drexel hosts St. Joseph's on Monday.
Colorado hosts Auburn on Monday in a game that doesn't tip off until 11 p.m. MT. It's part of a 24-hour college hoops marathon.