Lyon opted to forgo his senior season at Yale and signed an entry-level contract with the Philadelphia Flyers of the National Hockey League (NHL) on April 5, 2016.

[13] On February 18, 2018, Lyon recorded his first NHL win with the Flyers after replacing an injured Michal Neuvirth in the second period.

[14] On May 9, 2018, in a playoff win over the Charlotte Checkers, Lyon saved 94 of 95 shots faced in a record-setting 146 minutes 48 seconds, making it the longest game in AHL history.

[19] Following the 2020–21 season, his fifth within the Philadelphia Flyers organization, Lyon left as a free agent and was signed to a one-year, two-way contract with the Carolina Hurricanes on July 30, 2021.

With the Wolves, Lyon finished the regular season with 18 wins and 3 shutouts, earning him the Hap Holmes Memorial Award for the AHL goaltender with the lowest goals against average.

[28] Bobrovsky proceeded to lead the team to victory against the Bruins, and onward through the second and third rounds of the playoffs to the 2023 Stanley Cup Finals against the Vegas Golden Knights.

Lyon won bronze with the US National Team at the 2015 World Championships in the Czech Republic,[32] seeing action in one game during the tournament.

[34] After completing a 28-save shutout to give the Chicago Wolves the Calder Cup in 2022, Lyon was suspended for two games as the AHL's online stream captured him flipping double birds as celebratory photos were being taken.