The Cardinals (5-0) stayed perfect at their new downtown arena by swamping the overmatched Panthers (4-3) from the opening tip. Louisville scored the game's first 13 points and led by 33 at the half.
Eric Frederick led FIU with 12 points, but the Panthers missed their first seven shots, trailed by 20 less than nine minutes in and never threatened.
Knowles has been chastised recently by coach Rick Pitino for his poor conditioning and inability to get his teammates involved. Showing a renewed sense of urgency, the senior captain added six boards and three assists in his best game of the season.
The rest of the team wasn't bad either, particularly during the first half.
Knowles knocked down a pair of 3-pointers to start the game and the Cardinals soon took off. Louisville's defense harassed the Panthers into mistake after mistake and the Cardinals wasted little time taking advantage.
By the time FIU's Jeremy Allen hit a running bank shot with 13:03 to go in the first half, the Panthers already trailed 19-4.
Things never really got much better for FIU or coach Isiah Thomas, who spent most of the game watching from the bench in silence. Then again, there wasn't much to get excited about.
The Panthers shot 28 percent from the floor, turned it over 22 times and made just 2 of 13 3-pointers.
Louisville had no such issues. Knowles came into the game shooting just 29 percent from 3-point range, a number Pitino attributed to Knowles' habit of bypassing easy shots for ones with a hand in his face.
His selection wasn't that much better against the Panthers, but the results were. He made 4 of 8 from behind the arc against FIU, including one just before the halftime buzzer that gave Louisville a 48-15 lead at the break.
FIU played Florida State tough for a half in a loss to the Seminoles two weeks ago and had a chance to knock off Marshall on Monday before falling short in the final minute.
Yet the Panthers had no answer for the deeper, more talented Cardinals.
Louisville freshman guard Elisha Justice, who'd been told by Pitino to put it up more often, knocked down three 3-pointers during the Cardinals' opening deluge and finished with 12 points.
Dieng, a freshman center from Senegal, added five rebounds and seven blocks in his first extended playing time. Freshman guard Russ Smith, who missed the first four games with a foot injury, had four points in limited action.