INDIANAPOLIS -- Louisville refused to be accused again of lackluster defense on Saturday afternoon.

Three days after being embarrassed in an Atlantic Coast Conference home loss to No. 12 Virginia, the sixth-ranked Cardinals reasserted themselves to inflict the same suffocating humiliation on No. 16 Indiana for a 77-62 triumph in the Countdown Classic at Bankers Life Fieldhouse.

Coach Rick Pitino's players definitely got the message in holding the Hoosiers to 26 points below their seasonal point average. Cardinals sophomore forward Donovan Mitchell led the way, scoring a career-high 25 points off the bench.

"Coach let us have it and we took that to heart and said, 'We're not going to let Indiana come in here and embarrass us the way Virginia did,'" said Mitchell, an 11.5-point scorer who responded with an inspired effort in his first game as a reserve.

A 12-0 run near the end of the first half provided Louisville (12-2) with sufficient cushion and a 12-point halftime lead. Indiana (10-4) was unable to get closer than a six-point deficit after intermission.

In the final minutes, the Hoosiers were clearly frustrated on offense as they were repeatedly unable to get off shots until the final seconds of the shot clock. Indiana made just 19 of 59 (.322) while Louisville finished 27 of 51 (.529).

"That's a sign of just great defense," Mitchell said. "You start to get more excited as the clock goes down."

Pitino likened his team's effort to when Louisville knocked off No. 6 Kentucky prior to the Virginia loss.

"Just like the Kentucky game, we were great on defense, we did a lot of terrific things on offense and just got a big lift from Donovan, Deng (Adel) and especially Anas (Mahmoud)."

Adel, a sophomore forward, added 15 points. Mahmoud, a junior forward, made the most of his first start of the season with 10 points, two rebounds, two assists, three blocks and two steals. Pitino also credited Mahmoud with 10 defensive deflections.

Pitino said he challenged the benched Mitchell to play with more confidence, and it worked.

"You know starting doesn't mean anything," Pitino said, "but I just saw who wants to play like a star, and that means he's not counting his misses, he's someone that'll shoot every open shot, create and not worry about what the outside world thinks of his game."

That same outside world suddenly has reason to wonder about the defending Big Ten champions. Three days after losing 87-84 to Nebraska at home, Indiana struggled with 11 of 14 turnovers in the opening half, couldn't guard consistently and was never able to find an offensive rhythm.

"There's not too many times where we're going to shoot as bad as we did, so I don't think that we should just start focusing on offense more," said Hoosiers junior guard James Blackmon Jr. "I think it's going to come more from defense, and we've just got to focus in on that and follow the game plan a little better."

Blackmon, who averages a team-high 17.9 points, ended up with just 10 on 3-of-8 shooting. Junior guard Robert Johnson, who averages 14.2 points, made only 1 of 13 shots and missed all eight 3-point attempts. He scored seven of his nine points on free throws.

"The defensive part is where we lost it," said Indiana coach Tom Crean. "We didn't get up into the ball enough, whether it was a switch, whether it was over the screen, whatever the coverage was.

"Mitchell got hot. He's a really nice young man. We recruited him. I hope for his sake and their sake that he continues to play like that because obviously he played a little different than he's played of late."

Mitchell, who shot just 31.9 percent in the previous seven games, hit 8 of 15 shots overall and 4 of 8 3-pointers.

The Hoosiers' best player was also a starter who had been benched. Sophomore forward OG Anunoby scored 14 points in his first game as a reserve.

Tightly contested midway through the opening half, Louisville went ahead 21-20 on a Mahmoud inside basket. The 10th lead change proved to be the last as the Cardinals got hot and the Hoosiers stayed cold.

Just when Indiana appeared to have momentum, down 50-44 with 12:20 remaining, sophomore forward Juwan Morgan committed his team's 13th turnover, which led to a Mitchell 3-pointer. A short time later, Mitchell drained another 3-pointer to make it 58-46.

"We've just got to come together and know what type of team we are, have confidence in each other and just believe," Blackmon said.

NOTES: Hoosiers reserve freshman guard Devonte Green had a boot on his left foot and missed his first game of the season. ... This is the first in a three-game series, with next season's game at the Cardinals' KFC Yum! Center and a 2018 meeting at the Hoosiers' Simon Skjodt Assembly Hall in Bloomington. ... Louisville faced a ranked opponent for a third consecutive game. The Cardinals lost at home to No. 12 Virginia 61-53 and won at home against No. 6 Kentucky 73-70. Next up is a Wednesday ACC trip to No. 24 Notre Dame. ... The Hoosiers have a 10-8 lead in a series that began in 1921. The Cardinals won the most recent game 94-74 in the 2014 Jimmy V Classic at New York City. This was the third meeting at Indianapolis -- Louisville won 101-79 in 1988 and Indiana won 72-52 in 1990. ... Next up for the Hoosiers is a Big Ten game at home Tuesday against No. 14 Wisconsin.