Palacios, a senior and the lone contributing holdover from the Cardinals' 2005 Final Four team, is expected back from a torn ligament in his right knee by mid-December. Padgett, who hurt his knee Sunday, could be lost for the season.
That leaves Louisville with eight scholarship players and questions with depth. It runs an up-tempo offense and pressure defense and Pitino plans on doing more substituting than usual.
"We had to change our whole system overnight," coach Rick Pitino said. "Padgett was the key to our offense and how we ran the high and low."
In the interim, the Cardinals will rely on forward Derrick Caracter, who scored eight points and grabbed five rebounds before fouling out late, and a host of others to carry the load. Edgar Sosa added 10 points.
Louisville (3-0) led by double digits in the first half, but UNLV made four straight 3-pointers to take a 35-33 lead with 14:36 left.
Following a time out, Louisville scored the next nine points, including 3-pointers from Terrence Williams and Sosa, and never trailed again. The outburst was capped by a transition dunk from Clark as the Cardinals went on a decisive 16-2 run.
"We made an adjustment with our zone defense in that time out," Pitino said. "We couldn't stop them from making the 3, so we went to a man-to-man for the rest of the game."
Louisville, in town early for the Las Vegas Invitational on Friday and Saturday, will play formidable BYU in the semifinals and could meet No. 1 North Carolina in the finals.
Pitino said giving bench players crucial minutes against quality competition will be a benefit, but only if the Cardinals survive a tough nonconference schedule that includes a contest at instate rival Kentucky.
"If we get our guys back healthy it will make a lot of guys better," Pitino said. "When I made the schedule, I didn't think we'd be done to eight scholarship players."
UNLV (3-1), which had won its previous 19 games at home, got a team-high 11 points from Matt Shaw, the lone Rebel in double figures.
"Louisville is an outstanding team," UNLV coach Lon Kruger said. "Louisville turned it up a bit and made some good plays."