Holl was selected by the Chicago Blackhawks in the second round (No. 54) in the 2010 NHL Draft. He attended the University of Minnesota, where he had 38 points (eight goals, 30 assists) in 142 games during four seasons and helped the Golden Gophers advance to the NCAA Final in 2014.

After not signing with the Blackhawks following his collegiate career, Holl played most of the 2014-15 with Indy of the ECHL. He signed an AHL contract with Toronto for the 2015-16 season and had 21 points (five goals, 16 assists) in 60 games. On July 2, 2016, the Toronto Maple Leafs signed the free agent defenseman to a one-year, entry-level contract.

Holl had 19 points (eight goals, 11 assists) in 72 AHL games with Toronto in 2016-17. In 2017-18, he continued his improvement, as he had 28 points (seven goals, 21 assists) in 60 games and was named to the 2018 AHL All-Star Classic.

Holl was recalled by the Maple Leafs on an emergency basis on Jan. 31, 2018. He made his NHL debut and scored his first goal that night in a 5-0 win against the New York Islanders. He scored his second goal in as many games the next night in a 4-0 win against the New York Rangers, becoming the first Maple Leafs defenseman and sixth in NHL history to score a goal in each of his first two games.

On Feb. 3, 2018, he was returned to the AHL. He had five points (three goals, two assists) in 20 games to help Toronto win the Calder Cup for the first time.

The Maple Leafs signed Holl to a two-year contract on July 3, 2018. He played all of 2018-19 in the NHL, but played only 11 games and had one assist. He earned a bigger role in 2019-20 and finished with 18 points (two goals, 16 assists) and a plus-13 rating in 68 games, averaging 18:31 of ice time.

Holl signed a three-year, $10.2 million contract with the Detroit Red Wings on July 1, 2023. He was traded to the St. Louis Blues on March 6, 2026, after playing the season for Grand Rapids in the American Hockey League.