O'Byrne played 308 regular season and 25 playoff games in the NHL for the Montreal Canadiens, Colorado Avalanche, and Toronto Maple Leafs.

After attending his first Montreal training camp, O'Byrne was assigned to American Hockey League affiliate, the Hamilton Bulldogs, for the 2006–07 season.
As a stay-at-home defensive-defenceman, Ryan produced 12 assists in 80 regular-season games with the Bulldogs.
During the playoffs, he scored his first professional goal, which clinched the series over the Rochester Americans, advancing the Bulldogs to the Conference Semi-finals.
In the Championship Final, he then produced his second game-winning goal a game three win over the Hershey Bears en route to claiming the Calder Cup.

In the following 2007–08 season, O'Byrne made his NHL debut, recording two assists, in a 4–2 victory over the Boston Bruins on December 6, 2007.
Ryan missed a month of the season after suffering a broken thumb, before returning to health and scoring his first NHL goal in a 6–4 defeat to the San Jose Sharks on March 4, 2008.
He finished the season, while splitting time between Hamilton and Montreal, to finish with 33 games.

O'Byrne was then re-signed to a three-year contract with the Canadiens on July 16, 2008.
He made the Canadiens opening night roster for the 2008–09 season, appearing in 37 games for five assists, with two stints in the AHL.

In his second game of the 2009–10 campaign with the Canadiens, Ryan suffered a knee injury causing him to miss 20 games.
Upon his return, O'Byrne established himself as a regular within the defence corps.
On December 4, 2009, he changed his jersey number to 20 due to retiring of the number 3 in honour of Emile Bouchard for the Canadiens Centennial celebrations.
Similar to  Ray Bourque's homage to Phil Esposito in Boston, Ryan wore the number 20 jersey underneath his number 3 jersey and as a surprise, unveiled his new number during the banner hanging and presented Bouchard his jersey as a token of being the last to wear the number 3 for the Canadiens.
O'Byrne finished his first full NHL season, appearing in a career high 55 games and 13 post-season games as the Canadiens reached the Eastern Conference finals.

To begin the 2010–11 season, O'Byrne was a depth defenceman on the team's blueline.
In the final year of his contract he was traded by the Canadiens to the Colorado Avalanche for forward prospect Michael Bournival on November 11, 2010.
In his first game with the Avalanche, Ryan recorded a career high in ice time in a 5–1 win over the Columbus Blue Jackets on November 12, 2010.

During the 2012–13 NHL lockout, O'Byrne served as an assistant coach for the Victoria Grizzlies of the BCHL as a coach, but left the position to join the Florida Everblades of the ECHL to get some ice time and effectively work in his position as the NHLPA's representative for the Avalanche.
 He rejoined the Avalanche at the conclusion of the lockout.

In the midst of the 2012–13 season and in the final year of his contract at the trade deadline, O'Byrne was dealt by the Avalanche to the Toronto Maple Leafs in exchange for a fourth-round pick in the 2014 NHL Entry Draft on April 3, 2013.
On April 8, 2013, O'Byrne scored his first goal as a Maple Leaf.

His last NHL game was the Leafs-Bruins Game 7 in which the Leafs surrendered a 4–1 lead in the third period, and they would go on to lose 5–4 in overtime.

After experiencing a first round defeat to the Boston Bruins with the Leafs, O'Byrne was released to free agency.
O'Byrne agreed to his first contract abroad, signing a two-year contract with Czech-based HC Lev Praha of the Kontinental Hockey League on September 2, 2013.
In the 2013–14 season, O'Byrne enjoyed a largely successful season in Prague as a mainstay stay-at-home defenseman.
In 43 games he contributed with 2 goals and 9 points before helping Lev Praha advance to the Gagarin Cup finals in the playoffs.

O'Byrne's intention to fulfill the second year of his contract was terminated as Lev Praha declared bankruptcy and folded immediately in the off-season.
On July 7, 2014, he opted to remain i
O'Byrne played 308 regular season and 25 playoff games in the NHL for the Montreal Canadiens, Colorado Avalanche, and Toronto Maple Leafs.
After attending his first Montreal training camp, O'Byrne was assigned to American Hockey League affiliate, the Hamilton Bulldogs, for the 2006–07 season. As a stay-at-home defensive-defenceman, Ryan produced 12 assists in 80 regular-season games with the Bulldogs. During the playoffs, he scored his first professional goal, which clinched the series over the Rochester Americans, advancing the Bulldogs to the Conference Semi-finals. In the Championship Final, he then produced his second game-winning goal a game three win over the Hershey Bears en route to claiming the Calder Cup.
In the following 2007–08 season, O'Byrne made his NHL debut, recording two assists, in a 4–2 victory over the Boston Bruins on December 6, 2007. Ryan missed a month of the season after suffering a broken thumb, before returning to health and scoring his first NHL goal in a 6–4 defeat to the San Jose Sharks on March 4, 2008. He finished the season, while splitting time between Hamilton and Montreal, to finish with 33 games.
O'Byrne was then re-signed to a three-year contract with the Canadiens on July 16, 2008. He made the Canadiens opening night roster for the 2008–09 season, appearing in 37 games for five assists, with two stints in the AHL.
In his second game of the 2009–10 campaign with the Canadiens, Ryan suffered a knee injury causing him to miss 20 games. Upon his return, O'Byrne established himself as a regular within the defence corps. On December 4, 2009, he changed his jersey number to 20 due to retiring of the number 3 in honour of Emile Bouchard for the Canadiens Centennial celebrations. Similar to  Ray Bourque's homage to Phil Esposito in Boston, Ryan wore the number 20 jersey underneath his number 3 jersey and as a surprise, unveiled his new number during the banner hanging and presented Bouchard his jersey as a token of being the last to wear the number 3 for the Canadiens. O'Byrne finished his first full NHL season, appearing in a career high 55 games and 13 post-season games as the Canadiens reached the Eastern Conference finals.
To begin the 2010–11 season, O'Byrne was a depth defenceman on the team's blueline. In the final year of his contract he was traded by the Canadiens to the Colorado Avalanche for forward prospect Michael Bournival on November 11, 2010. In his first game with the Avalanche, Ryan recorded a career high in ice time in a 5–1 win over the Columbus Blue Jackets on November 12, 2010.
During the 2012–13 NHL lockout, O'Byrne served as an assistant coach for the Victoria Grizzlies of the BCHL as a coach, but left the position to join the Florida Everblades of the ECHL to get some ice time and effectively work in his position as the NHLPA's representative for the Avalanche.  He rejoined the Avalanche at the conclusion of the lockout.
In the midst of the 2012–13 season and in the final year of his contract at the trade deadline, O'Byrne was dealt by the Avalanche to the Toronto Maple Leafs in exchange for a fourth-round pick in the 2014 NHL Entry Draft on April 3, 2013. On April 8, 2013, O'Byrne scored his first goal as a Maple Leaf.
His last NHL game was the Leafs-Bruins Game 7 in which the Leafs surrendered a 4–1 lead in the third period, and they would go on to lose 5–4 in overtime.
After experiencing a first round defeat to the Boston Bruins with the Leafs, O'Byrne was released to free agency. O'Byrne agreed to his first contract abroad, signing a two-year contract with Czech-based HC Lev Praha of the Kontinental Hockey League on September 2, 2013. In the 2013–14 season, O'Byrne enjoyed a largely successful season in Prague as a mainstay stay-at-home defenseman. In 43 games he contributed with 2 goals and 9 points before helping Lev Praha advance to the Gagarin Cup finals in the playoffs.
O'Byrne's intention to fulfill the second year of his contract was terminated as Lev Praha declared bankruptcy and folded immediately in the off-season. On July 7, 2014, he opted to remain i
Ryan O'Byrne