Internationally, Pastrňák has played for the Czech national team at both the junior and senior level, including at four World Championships.

[1][11] For the 2013–14 season, Pastrňák was promoted to Södertälje SK's senior team in Allsvenskan, Sweden's second-highest professional league.

He led his team in points, scoring 8 goals and 16 assists in 36 games, though he missed part of the season due to a concussion.

He made his NHL debut with the Bruins on 24 November, logging 7:53 of ice time in a 3–2 overtime loss to the Pittsburgh Penguins.

[13] On 29 March, Pastrňák became the youngest Bruins' player in history to score an overtime, game-winning goal in regular season play in Boston's 2–1 road win over the Carolina Hurricanes.

On 28 October 2016, Pastrňák was suspended two games for an illegal check to the head of New York Rangers defenceman Dan Girardi.

[19][20] Towards the end of the 2017–18 season, on 13 March 2018, Pastrňák scored his first NHL hat-trick during a come-from-behind 6–4 Bruins' road win over the Carolina Hurricanes.

[21] On 14 April, Pastrňák recorded another hat-trick along with three assists in a 7–3 home win over the Toronto Maple Leafs in game two of the Bruins' first round series during the 2018 playoffs.

[22] He also became the youngest player in NHL history to score six points in a single playoff game beating Wayne Gretzky's record.

[24] On 16 January 2019, in a game against the Philadelphia Flyers, Pastrňák became the all-time leader for most goals in Boston Bruins history before the age of 23 passing Barry Pederson.

In the first game in the second round of the 2021 playoffs, he scored a hat trick against the New York Islanders to help give the Bruins a 1–0 series lead on 29 May.

The Bruins won the Presidents' Trophy as the best team of the regular season, breaking the league record for both wins and standing points.

[38] On 4 April 2024, Pastrňák scored the 60th game-winning goal of his career against the Carolina Hurricanes, tying him with Ray Bourque for the fifth most in Bruins history.

Following the Bruins' defeat by the Tampa Bay Lightning in the Second Round of the 2018 playoffs, Pastrňák was invited to participate at the 2018 IIHF World Championship.

[40] He played at the 2024 IIHF World Championship with Czechia and won a gold medal, scored the winning goal in the final and was also named player of the game.