The following month, after solid performances in the Swedish Hockey League and internationally for Sweden in the Under 18 and World Junior tournaments, the butterfly style goaltender[2] was selected 31st overall in the 2008 NHL entry draft as the first choice of the Florida Panthers.

[4] On 23 January 2011, Markström made his NHL debut at the Prudential Center in Newark when he replaced starter Scott Clemmensen at the start of the second period in a loss against the New Jersey Devils.

After surgery in South Florida, Markström worked to get back in the game, hoping to have a real shot at the NHL level.

With Tomáš Vokoun departing via free agency for the Washington Capitals, Markström attended Florida's September 2011 training camp to compete for a starting or backup position with fellow goaltenders José Théodore and Scott Clemmensen, ultimately being awarded the backup role when Clemmensen was injured.

[6] On 22 October, Markström earned his first NHL win when he played in the third period against the New York Islanders and made 18 saves on 18 shots.

Following an injury to Ryan Miller, Markström was recalled to the Canucks to serve as backup to Eddie Läck and got to play on 3 March 2015, against the San Jose Sharks, but was pulled after he allowed three goals on four shots.

On 3 January 2020, Markström was named to his first NHL All-Star Game, replacing the Vegas Golden Knights' goaltender Marc-André Fleury.

On 9 October 2020, Markström left the Vancouver Canucks as a free agent and signed a six-year, $36 million contract with the Calgary Flames.

[13] He finished with a record of 22–19–2 in 43 games in the pandemic-shortened 2020–21 season, having struggled with a concussion midway through following a collision with Canucks forward Tanner Pearson that was initially undiagnosed.

[16] The Flames won the Pacific Division, and advanced into the 2022 Stanley Cup playoffs to meet the Dallas Stars in the first round.

[19] On 19 June 2024, Markström was traded to the New Jersey Devils in exchange for defenceman Kevin Bahl, and a 2025 first-round draft pick.

Named the backup goaltender, Markström played Sweden's opening game of the tournament after starter Henrik Lundqvist missed it due to an illness.