Kyle Okposo was selected by the New York Islanders with the No. 7 pick in the 2006 NHL Draft after scoring 27 goals in 50 games for Des Moines of the United States Hockey League.

Okposo enrolled the following season at the University of Minnesota, where he had 40 points (19 goals, 21 assists) in 40 games as a freshman. Although he returned to the Golden Gophers as a sophomore, Okposo left midway through the season to sign an entry-level contract with the Islanders on Dec. 19, 2007.

Okposo would go on to play 35 games for Bridgeport of the American Hockey League, where he had 28 points (nine goals, 19 assists), before earning a call-up at the end of the 2007-08 season. He made his NHL debut against the Toronto Maple Leafs on March 18, 2008, before scored his first NHL goal and assist in a 3-1 win against the New Jersey Devils three days later.

Okposo finished the season with five points (two goals, three assists) in nine games then followed it up by leading the Islanders with 18 goals as a 20-year-old in 2008-09. He also led New York and all NHL rookies with 76 takeaways that season.

Named an alternate captain ahead of the 2009-10, Okposo scored 19 goals and finished second on the team with 52 points.

After three more seasons in New York, Okposo broke out in 2013-14, when he set an NHL career high in goals (27), assists (42) and points (69). Despite missing 22 games because of a detached retina that required surgery, Okposo finished second on the Islanders with 51 points (18 goals, 33 assists) in 2014-15, including scoring four goals against the Pittsburgh Penguins on Jan. 16, 2015.

Okposo again finished second on the Islanders with 64 points (22 goals, 42 assists) the following season, and on July 1, 2016, he signed a seven-year contract with the Buffalo Sabres as a free agent.

During his first season with the Sabres, Okposo had 45 points (19 goals, 26 assists) in 65 games and played in the 2017 NHL All-Star Game.

Okposo, named Sabres captain Oct. 8, 2022, played his 1,000th game in the NHL on Nov. 14, 2023, a 5-2 loss to the Boston Bruins at KeyBank Center. He was traded to the Florida Panthers on March 8, 2024 for defenseman Calle Sjalin and a conditional pick in the 2024 NHL Draft.

Prior to the 2024 Stanley Cup Playoffs, Okposo did not play in the NHL postseason since 2016 with the Islanders. He had two assists in 17 playoff games for the Panthers to become a first-time Stanley Cup champion.

Okposo announced his retirement from the NHL on Sept. 19, 2024, after 17 seasons. He got his day with the Cup in July in his home state of Minnesota after a delay because of an international IT outage, which cancelled a public event he had schedule, but he still got to spend time with the Cup and his family.