Selected by the Buffalo Sabres with No. 8 pick in the 2013 NHL Draft following his second season with his hometown team (TPS Turku) in Liiga, Finland's top professional league, Ristolainen wasted no time making the NHL.

Immediately coming over to North America, Ristolainen made the Sabres out of training camp and made his NHL debut as an 18-year-old defenseman against the Detroit Red Wings on Oct. 2, 2013. He recorded his first NHL point, a goal, later that month in a 3-1 win against the Florida Panthers on Oct. 25, but he ultimately split the season between Buffalo and Rochester of the American Hockey League. In 34 NHL games, he had two goals and two assists.

Ristolainen also played for Finland in the 2014 World Junior Championship, where he scored three goals in five games, including the winner in overtime against Sweden in the gold-medal game.

Ristolainen stayed with the Sabres in 2014-15, getting 20 points (eight goals, 12 assists) in 78 games. But he made a big jump the following season, when he led Buffalo defensemen in goals (nine), assists (32) and points (41) in 82 games while averaging 25:17 of ice time.

Ristolainen continued to produce for the Sabres, getting at least 41 points and leading the team in ice time in each of the next three seasons, but with Buffalo missing the Stanley Cup Playoffs each season, there was speculation about whether he would try and be traded.

Instead, Ristolainen said he wanted to help the Sabres qualify for the playoffs, and although they fell short again in 2019-20, there were signs of improvement, most noticeably on defense. After having an NHL worst minus-41 rating in 2018-19, Ristolainen was minus-2 before the season was paused March 12 due to concerns surrounding the coronavirus.

Ristolainen was traded to the Philadelphia Flyers by the Sabres on July 23, 2021. He signed a five-year, $25.5 million contract with the Flyers on March 10, 2022, and was named to Team Finland's roster for the Olympic Winter Games Milano Cortina 2026.