Holden ended his major junior hockey career by signing a three-year entry-level contract with the Columbus Blue Jackets.

In his final season with the team, he played in 35 games and recorded 22 points, the most by a defenseman, which drew attention from the Alberta Junior Hockey League (AJHL).

[5] During the 2005 AJHL Championship, Holden and the Kodiaks lost 3–2 against the Weyburn Red Wings of the Saskatchewan Junior Hockey League (SJHL).

[6] Holden eventually played Junior A-level hockey for the Kodiaks and Sherwood Park Crusaders in the AJHL,[7] but disliked the attention he received.

[9] As a result, Holden flew under the radar of most scouts until Chilliwack Bruins General manager Darrell May saw him play for the Kodiaks the night before the 2006 Western Hockey League (WHL) Entry Draft.

"[10] After his rookie season, Holden earned a scholarship to the University of the Fraser Valley[11] and was invited to the Edmonton Oilers 2007 NHL training camp on an Amateur Tryout.

On March 28, 2008, Holden signed a three-year entry-level contract with the Columbus Blue Jackets, thus concluding his major junior career.

[14] Upon signing his contract, Holden joined the Columbus Blue Jackets then-American Hockey League (AHL) affiliate, the Syracuse Crunch, for the remainder of the 2007–08 season.

[28] On July 5, 2013, Holden left the Blue Jackets organization and signed a two-year contract as a free agent with the Colorado Avalanche.

[29] After partaking and impressing in his first Avalanche training camp, Holden was unexpectedly successful in making the team's opening night roster for the 2013–14 season.

[30] Holden sat as a healthy scratch in the first 11 games of the season before making his Avalanche debut as a forward in a 3–2 overtime victory over the Dallas Stars on November 1, 2013.

[32] In returning to his natural position of defence, Holden scored his first career NHL goal, a game-winner, against Braden Holtby in a 4–1 victory over the Washington Capitals on November 10, 2013.

[35] He also led all Avalanche defenceman with three goals and four points in their Western Conference Quarter-final series defeat in the 2014 Stanley Cup playoffs against the Minnesota Wild.

[39] Numerously throughout the season, Holden was called upon to serve at the Avalanche's fourth line forward with teammates Marc-André Cliche and winger Cody McLeod.

[42] On June 25, 2016, with two years remaining on his contract, Holden was traded by the Avalanche at the 2016 NHL Entry Draft to the New York Rangers in exchange for a 4th-round pick in 2017.

[44] He often played on the right side for the Rangers due to their depleted defense, and spent time on both the second and first top pairings with Marc Staal and Ryan McDonagh.

[47] Accurately so, Holden played only 55 games for the Rangers while in the final year of his contract before being traded to the Boston Bruins in exchange for Rob O'Gara and a 2018 third-round draft pick.

[53] At the 2020 NHL Trade Deadline, Vegas rewarded Holden's play with a two-year, $3.4 million contract extension; preventing him from becoming an unrestricted free agent at the end of the 2019–20 season.