Donato made an immediate impression with the Boston Bruins in his NHL debut on March 19, 2018. After starring for the United States at the 2018 PyeongChang Olympics and at Harvard University, Donato had three points (one goal, two assists) playing left wing with center David Krejci and right wing Danton Heinen in a 5-4 overtime loss to the Columbus Blue Jackets.

"During warm-ups, it kind of felt like a dream," Donato said after the game. "I didn't really get that warmed up because I was too focused on everything else and just kind of the whole situation."

Donato was still enrolled at Harvard when he signed a two-year contract with the Bruins on March 18. He completed his junior season leading the Crimson with 43 points (26 goals, 17 assists) in 29 games and was a finalist for the Hobey Baker Award, given to the top player in NCAA Division I hockey.

The son of former Bruins forward and NHL veteran Ted Donato -- also the coach at Harvard -- Ryan was chosen in the second round (No. 56) in the 2014 NHL Draft. He scored five goals in seven games in PyeongChang before the U.S. was eliminated in a 3-2 shootout loss to the Czech Republic in the quarterfinals.

His time with the Bruins ended on Feb. 20, 2019, when he was traded to the Minnesota Wild for forward Charlie Coyle. He had 16 points (four goals, 12 assists) in 22 games with Minnesota after the trade, then earned a regular role with the Wild in 2019-20.

Donato signed with the expansion Seattle Kraken as a free agent Sept. 13, 2021. He scored the first regular-season goal in Kraken history in their first game, a 4-3 loss to the Vegas Golden Knights on Oct. 12, 2021. Donato signed a one-year, $1.2 million contract to stay with the Kraken on July 27, 2022 after scoring an NHL career-high 16 goals the previous season.

Donato signed a two-year, $4 million contract with the Chicago Blackhawks on July 1, 2023. Two seasons later he scored an NHL career-high 31 goals and signed a four-year, $16 million contract with the Blackhawks on June 18, 2025.