He played for the Buffalo Sabres, Carolina Hurricanes, Los Angeles Kings, Edmonton Oilers and Dallas Stars of the National Hockey League (NHL).

[11] During this time, he recorded his first career NHL goal on 28 November against St. Louis Blues' goaltender Manny Legace in a 4–3 loss.

[12] In December, Sabres' coach Lindy Ruff announced that Sekera would remain on the NHL roster following further injuries to Dmitri Kalinin and Henrik Tallinder.

[1] Sekera was once again named to the Sabres' opening night roster to begin the 2009–10 season and played in three games before suffering a rib injury.

[20] During the 2012–13 NHL lockout, which canceled the majority of the first half of the 2012–13 season, Sekera played in his native Slovakia with Slovan Bratislava of the Kontinental Hockey League (KHL).

[22] Through his first season with the Hurricanes, Sekera played alongside defensive partner Justin Faulk and recorded new career-highs in goals and points.

[23] He finished the 2013–14 season with a new career-best 44 points while leading all Hurricanes skaters in blocked shots and average time on ice per game.

[29] He was eventually traded to the Los Angeles Kings in exchange for a conditional first-round draft pick and defensive prospect Roland McKeown on 25 February.

[30] On 1 July 2015, Sekera left the Los Angeles Kings to sign a six-year, $33 million contract with the Edmonton Oilers.

[1] Sekera continued to heal from his torn ACL during the 2017 off-season and made his 2017–18 season debut on 22 December in a 3–2 win over the St. Louis Blues.

[39] However, his return to the lineup was shortlived as he was placed on injured reserve in February 2018 after taking a puck to the face during a game against the Anaheim Ducks.

[42] In the 2018–19 season, following a lengthy rehab, Sekera returned to play on a conditioning assignment with AHL affiliate the Bakersfield Condors, on 5 February 2019.

[43] After five games, Sekera returned to the Oilers and made his first appearance with Edmonton in over a year, playing a third-pairing defensive role against the Arizona Coyotes on 19 February 2019.

[50] Adding a veteran presence to the Stars' third pairing on the blueline,[47] Sekera appeared in 57 games in the 2019–20 season and posted two goals and six assists.

During the Final series against the Tampa Bay Lightning, Sekera blocked a shot in the first period in Game 5 and left the ice until overtime.

[52] In the playoffs, Sekera appeared in a career high 27 postseason games, adding one assist, in helping the Stars reach the 2020 Stanley Cup Finals.

[54] As the Stars pushed to qualify for the 2021 Stanley Cup playoffs, Sekera was struck by a puck and named a game-time decision for the following game against the Columbus Blue Jackets.

However, as a result of their slow start, Sekera, Jacob Peterson, and Riley Tufte were placed into the lineup as a replacement for Blake Comeau, Joel Kiviranta, and Thomas Harley on 14 November.

[59] He returned to the senior national team for the 2009 IIHF World Championship, where he finished with two points in 10 games as Slovakia failed to qualify to the next round.

[60] Following another unsuccessful tournament, Sekera was named to Slovakia's 2010 Winter Olympics roster for the first time and competed at the 2010 IIHF World Championship.

He played with Boston Bruins defenceman Zdeno Chara throughout the tournament as Slovakia's top pairing but the team failed to medal.