At 6-foot-8, Myers is one of the tallest players in NHL history. But his talent, more than his size, is what helped the Houston-born, Calgary-raised defenseman stand out. In junior hockey, Myers won Western Hockey League playoff MVP honors for helping Kelowna to the 2009 WHL championship and was a Memorial Cup All-Star that year.

His long stride is fluid and efficient, enabling the player teammates dubbed "The Big Easy" to quickly get up and down the ice. He is not an overly physical presence; he combines his size and reach with good positioning gained via his speed to get the upper hand on opponents.

A first-round pick (No. 12) by the Buffalo Sabres in the 2008 NHL Draft, Myers made his NHL debut at age 19 when Buffalo hosted the Montreal Canadiens in its season-opener Oct. 3, 2009. He played in all 82 games during the 2009-10 season, one of four rookies to do so (Artem Anisimov, Jamie Benn, John Tavares), and led first-year players in average ice time (23:44), assists (37) and blocks (137) while finishing third among rookies in points (48).

Myers also led the Sabres in ice time, ranked first among Buffalo defensemen in goals (11), assists, points and blocks, and won the Calder Trophy voted as the top rookie in the NHL. He made his Stanley Cup Playoff debut that season, scoring one goal and leading Sabres defensemen in shots (18) while playing in all six games of Buffalo's first-round loss to the Boston Bruins.

The next season, Myers again led Buffalo defensemen in scoring (37 points) and tied forward Thomas Vanek for the team lead with five game-winning goals. After he signed a seven-year contract with the Sabres on Sept. 15, 2011, injuries, including a broken leg, hampered him for the next two seasons.

Myers was traded to the Winnipeg Jets on Feb. 11, 2015 in a deal that sent forward Evander Kane to Buffalo. He scored 15 points in 24 games to help the Jets qualify for the playoffs for the first time since the franchise relocated to Winnipeg for the 2011-12 season. In the playoffs, Myers scored one goal and led Jets skaters in average ice time (24:23) over the four games of their loss to the Anaheim Ducks in the Western Conference First Round.

Myers signed a five-year contract with the Vancouver Canucks on July 1, 2019 after five seasons playing for the Jets. He had 29 points (five goals, 24 assists) and was plus-16 in 77 games of the 2023-24 season to help the Canucks make the playoffs for only the second time since 2015-16. He signed a three-year, $9 million contract with Vancouver on June 27, 2024, and played his 1,000th NHL game Oct. 19, a 3-2 win against the Philadelphia Flyers at Wells Fargo Center.

Myers was traded to the Dallas Stars on March 4, 2026.