Athanasiou was selected by the Detroit Red Wings in the fourth round (No. 110) of the 2012 NHL Draft after scoring 59 points (33 goals, 26 assists) in 120 games in the Ontario Hockey League for his hometown team, London.

Prior to the 2012-13 season, London traded Athanasiou to Barrie. He broke out for 67 points (29 goals, 38 assists) in 66 games that season and helped Barrie advance to the OHL finals. Athanasiou finished with 25 points (12 goals, 13 assists) in 22 playoff games.

Before making the jump to professional hockey, Athanasiou scored an OHL career-high 95 points (49 goals, 46 assists) in 66 games in 2013-14, his final season in Barrie. Having signed a three-year, entry-level contract with Detroit on Nov. 15, 2013, he played two games with Grand Rapids in the American Hockey League after Barrie's season ended.

In 2014-15, his first full season with Grand Rapids, Athanasiou had 32 points (16 goals, 16 assists) in 55 regular-season games. He scored nine points (five goals, four assists) in 16 playoff games and helped Grand Rapids reach the conference finals.

Athanasiou made his NHL debut for the Red Wings at home against the Dallas Stars on Nov. 8, 2015. He got his first NHL point two days later, scoring a goal in a 1-0 home victory against the Washington Capitals.

The Red Wings sent Athanasiou back to Grand Rapids after six games, and he finished with 16 points (eight goals, eight assists) in 26 AHL games. Detroit brought him back in February, and he ended the season with 14 points (nine goals, five assists) in 37 NHL games.

He played his first full NHL season with the Red Wings in 2016-17, finishing with 29 points (18 goals, 11 assists) in 64 games. Athanasiou was second on Detroit in goals behind forward Tomas Tatar (25) despite playing 18 fewer games.

Athanasiou was traded by the Red Wings to the Edmonton Oilers on Feb. 24, 2020. After two seasons with the Los Angeles Kings, he signed a one-year contract with the Chicago Blackhawks on July 13, 2022, and a two-year contract June 8, 2023.