Frolík made his NHL debut for Florida during the 2008–09 season, in which he finished with 21 goals and 24 assists for 45 points in 79 games played. Frolik recorded 43 points the following season.
Chicago Blackhawks
On 9 February 2011, during Frolík's third season with the Panthers, in 2010–11, he was traded to the Chicago Blackhawks in exchange for Jack Skille, Hugh Jessiman and David Pacan. Frolík scored his first goal as a Blackhawk on 2 March 2011, against the Calgary Flames. On 24 April, he scored the first Stanley Cup playoffpenalty shot in Blackhawks history against goaltender Cory Schneider of the Vancouver Canucks in Game 6 of the Western Conference Quarterfinals. On 15 July 2011, Frolík signed a three-year contract extension with the Blackhawks at an annual average value at $2.333 million. During the 2012–13 NHL lockout, Frolík played for Piráti Chomutov of the Czech Extraliga. On 27 May 2013, during the 2013 playoffs, he scored the second playoff penalty shot goal of his career, against Jimmy Howard of the Detroit Red Wings, becoming the first player in NHL history to score more than one career penalty shot goal in the playoffs. He ultimately scored ten points in the playoffs en route to the Blackhawks' Stanley Cup victory over the Boston Bruins in six games.
Winnipeg Jets
In the subsequent off-season, on 30 June 2013, Frolík was traded to the Winnipeg Jets in exchange for a third- and fifth-round pick at the 2013 NHL Entry Draft. In the 2013–14 season opener on 2 October 2013, at Rexall Place against the Edmonton Oilers, Frolík scored twice in a 5–4 Winnipeg win. On 29 July 2014, Frolík and the Jets agreed on a one-year, $3.3 million contract. He finished with 19 goals and 23 assists on in the regular season, but was held pointless during the Jets' four-game sweep at the hands of the Anaheim Ducks in the 2015 playoffs.
Calgary Flames
On 1 July 2015, Frolík, as an unrestricted free agent, signed a five-year, $21 million contract with the Calgary Flames at an annual average value of $4.3 million.
Buffalo Sabres
During his final year under contract with the Flames in the 2019–20 season, unable to replicate his offensive production from previous years with 10 points through 38 games, Frolik was traded by the Flames to the Buffalo Sabres in exchange for a fourth round pick in 2020 on January 2, 2020.
Personal life
His partner is former Miss Czech Republic 2001, Czech model and TV/radio personality Diana Kobzanova. They have two daughters together.