Terrence Williams had 20 points, eight assists and five rebounds and Samardo Samuels had 21 points and 12 boards for the Cardinals (6-1), who used a 17-2 burst midway through the second half to take control.
Wes Channels led Austin Peay (5-3) with 23 points and Drake Reed added 18 points and five rebounds but the Governors came undone during a 5-minute stretch in the second half.
Austin Peay led 59-54 with 13 minutes to play, but Louisville responded with the kind of offensive avalanche that has made the Cardinals a trendy Final Four pick.
Knowles knocked down three 3-pointers and added a runner and a free throw as the Cardinals rallied. He capped the run with a 3-pointer from the wing that gave Louisville an 81-65 lead with 5 minutes remaining. The sophomore guard was 8-of-11 from the field, including 4-of-5 3-pointers in 21 energetic minutes.
The Cardinals needed just about every one of them after an uncharacteristically lifeless defensive performance, at least for the game's first 30 minutes.
Louisville's win over the Governor's.
Louisville had rolled to five straight easy wins at Freedom Hall to open the season, winning by an average of 34 points. The Governors, picked to finish third in the Ohio Valley Conference, were hardly intimidated.
Louisville had been holding opponents to 34 percent shooting, but the Governors weren't exactly bothered by the myriad of defenses the Cardinals threw at them. Austin Peay shot 48 percent from the field but lost its composure during Louisville's run. The Governors turned the ball over 18 times and went cold as soon as the Cardinals got hot.
Knowles led the way, hitting consecutive 3-pointers early in Louisville's run and using his quick hands to help disrupt Austin Peay's guards.
Knowles' shooting allowed the Cardinals to push the tempo and helped free things up for Samuels. The freshman missed four of his first five shots during a miserable first half but made up for it with a handful of dunks in the second half, including a thunderous jam with a minute left as the Cardinals exhaled.
For long stretches, however, the Cardinals and Freedom Hall held their breath as the Governors gave Louisville all it could handle.
Reed, who often had two or three bodies flying at him whenever he touched the ball, kept finding ways to get his unorthodox shot off.
The two-time All-OVC player seemed to befuddle the Cardinals with his funky delivery. Raising his right arm straight above his head, Reed's shot was almost impossible to block despite the best efforts of whichever Cardinal appeared to be in the vicinity.
Reed even knocked down his second 3-pointer of the season and the 10th of his career during the first half as the Governors managed to keep the lethargic Cardinals close, trailing 41-39 at halftime.