Ekman-Larsson began his career at Tingsryds AIF club of the HockeyAllsvenskan during the 2007–08 season, recording eight points in 27 games.

Ekman-Larsson recorded his first NHL point through an assist on a Kyle Turris goal in a 4–3 overtime win against the Carolina Hurricanes on 23 October 2010.

Two days later, he then recorded his first NHL playoff assist and point on a goal by Antoine Vermette as the Coyotes lost to the Blackhawks 4–3 to even the series.

For the duration of the 2012–13 NHL lockout, Ekman-Larsson, who was on the last year of his entry-level contract, was assigned to Phoenix's American Hockey League (AHL) affiliate, the Portland Pirates.

Initially credited to teammate Martin Hanzal, after further review the goal was shown to bounce off a Dallas player and into the net.

[18] In the 2016–17 season, on 18 March 2017, during a game against the Nashville Predators, Ekman-Larsson scored his 40th career powerplay goal, tying Fredrik Olausson for the most by a defenceman in Winnipeg Jets/Arizona Coyotes history.

[19] On 3 April, with the Coyotes out of playoff contention, Ekman-Larsson was granted a leave of absence for the remaining three regular seasons games in order to return to his native Sweden due to the death of his mother, following a prolonged battle with cancer.

[23] After the regular season concluded and the Coyotes again failed to make the playoffs, Ekman-Larsson was nominated for the King Clancy Memorial Trophy, awarded to the player who best exemplifies leadership qualities on and off the ice and gives back to his community, ultimately ceding the award to both Henrik and Daniel Sedin of the Vancouver Canucks.

[24] On 1 July 2018, Ekman-Larsson signed an eight-year, $66 million contract extension with the Coyotes; he was set to become a free agent the following season.

[30] On 7 April 2022, Ekman-Larsson played his first game against the Arizona Coyotes as a Canuck and got an assist in a 5–1 win on a goal by Alex Chiasson.

[35] Injuries to Brandon Montour and Aaron Ekblad led to increased ice time, which along with chemistry with Gustav Forsling promoted Ekman-Larsson to the Panthers' top power play unit.

[42] Ekman-Larsson's maternal grandfather, Kenneth Ekman,[43] also a defenceman, was selected to represent Sweden in the 1972 Winter Olympics.

[45] Ekman-Larsson's younger brother, Kevin, was previously signed with the Coyotes' AHL affiliate, the Tucson Roadrunners.

[50] In 2021, he sold his $6.5 million house in North Scottsdale to Milwaukee Brewers left fielder Christian Yelich.