The 6-foot-8 forward had 18 points, 13 rebounds and three blocked shots to help the 18th ranked Cardinals to 76-64 win on the road against the Huskies on Saturday night.
He hit eight of his 10 shots and was a big part of the Cardinals' 45-30 rebounding advantage.
"We rebounded a team, that was what it really was about," Harrell said. "On the defensive end, we limited that team to one shot and on the offensive end we were giving ourselves second and third chances."
Russ Smith scored 18 of his 23 points in the second half as the Cardinals pulled away to win for the fifth time in six games.
"It definitely was a Top-25 environment, so this was a great win," said Smith.
Shabazz Napier had a career high 30 points to lead Connecticut (14-4, 2-3), which was coming off a win Thursday at No. 17 Memphis.
The game included Kevin Ollie's first ejection as UConn's head coach. He picked up two quick technical fouls in the second half after a no-call in front of the UConn bench.
Louisville led 34-28 at halftime, but UConn erased that deficit in the first 2 minutes of the second half. A 3-pointer by Napier tied the game at 34.
Louisville then used a 20-4 run to pull away, and held on.
Smith's driving layup and free throw made it 45-34.
Ollie was given a technical a short time later. He lost control after official Mike Stuart failed to call anything when Wayne Blackshear and Niels Giffey collided in front of the UConn bench as Giffey was shooting. Louisville made two of the four free throws to go up 49-38.
"I don't know if it was warranted or not warranted," Ollie said. "They gave me the first "T" and I really didn't have a chance to do anything and then the second one came.
The Cardinals stretched that lead to 54-38 on a reverse layup by Blackshear before Tyler Olander snapped the run with a layup.
Connecticut began chipping away, and cut the deficit to seven when Napier made a 3-pointer with 2:38 left.
But Smith had seven points in the last 2 minutes, and Louisville held on.
"I just thought we had to have good team defense, good rebounding and I felt if we took care of the ball, we was going to win," Napier said. "We didn't do all of that."
The Cardinals quickly took control underneath. Ten of Louisville's first 12 points came in the paint.
Harrell hit seven of his eight first-half shots and had 15 points, six rebounds and three blocked shots before the break.
"I didn't try to force anything, or go for a career high in scoring," Harrell said. "I just took what the defense gave me and made it work."
A layup by Luke Hancock gave the Cardinals a 21-13 lead midway through the first half.
Napier, who scored more than 20 points for the sixth time this season, kept the Huskies in striking distance. He had 11 points in the half, but the Cardinals went into the break with a 34-28 lead.
UConn's DeAndre Daniels, who had scored in double figures in five straight games, sat for most of the first half with two fouls. He finished with just three points.
UConn's 7-foot center Amida Brimah had two blocked shots and now has 50 on the season.
Connecticut had won three straight after dropping its first two conference games on the road in Texas to Houston and SMU.
Louisville guard Chris Jones missed his second straight game with an oblique injury. Freshman Terry Rozier started in his place and had five points.
Louisville is 5-1 since Chane Behanan was dismissed from the team last month. The Cardinals also have been playing without Kevin Ware, who has been redshirted after struggling to come back from last year's devastating leg injury sustained in the Midwest regional final against Duke.
"Our last three games, We're really starting to play good basketball," said coach Rick Pitino. "Our defense has picked up, our rebounding has picked up."
UConn point guard Ryan Boatright was playing his second straight game since the death of his 20-year-old cousin Arin Williams, who was shot and killed Monday in Boatright's hometown of Aurora, Ill.
Williams' mother died in childbirth, and he and Boatright were raised as brothers in Boatright's home. The UConn junior had 10 points, but made just four of his 14 shots.
Ollie said the guard will be heading to Chicago to spend the next few days with his family.
UConn hadn't lost at Gampel Pavilion since being beaten by a point in double overtime by Georgetown last February.