Gagner did something no other NHL player in the 21st century has accomplished: score eight points in a regular-season game. He scored four goals and assisted on four others for the Edmonton Oilers against the Chicago Blackhawks on Feb. 2, 2012, becoming the first NHL player to do so since Mario Lemieux for the Pittsburgh Penguins (five goals, three assists against the New Jersey Devils on Dec. 31, 1988). He also became the second player in NHL history (Lemieux) with eight points in a game when his team scored exactly eight goals.

The son of retired NHL forward Dave Gagner was the Oilers' first pick (No. 6) in the 2007 NHL Draft. Although Sam Gagner scored between 13 and 18 goals and 41 and 49 points in each of his first five seasons with the Oilers, he was traded to the Tampa Bay Lightning, and one hour later to the Arizona Coyotes, on June 29, 2014.

Gagner played one season each for the Coyotes and Philadelphia Flyers before scoring 18 goals and an NHL career-high 50 points for the Columbus Blue Jackets in 2016-17. He signed a three-year contract with the Vancouver Canucks on July 1, 2017, was traded back to the Oilers on Feb. 16, 2019, and to the Detroit Red Wings on Feb. 24, 2020.

Gagner returned for his 16th NHL season by signing with the Winnipeg Jets on Sept. 2, 2022. He played his 1,000th NHL game Dec. 29, a 4-2 victory against the Canucks in Winnipeg. He started his 17th season with a return to the Oilers after signing a one-year, $775,000 contract Oct. 31, 2023, following a professional tryout during training camp. Gagner had 10 points (five goals, five assists) in 27 games before the Oilers placed him on waivers March 5 for the purpose of assignment to Bakersfield of the American Hockey League.

Gagner was named director of player development for the Ottawa Senators on May 15, 2025, after ending his playing career. He had 529 points (197 goals, 332 assists) in 1,043 games over 17 seasons and four assists in 11 Stanley Cup Playoff games with the Flyers and Blue Jackets. Gagner completed his professional career with 10 assists in 19 games for Ottawa's AHL affiliate in Belleville.