A veteran of six CFL seasons, Murphy says he feels he's accomplished all his goals on the football field.
Murphy, who won a Grey Cup with the B.C. Lions in 2006, was a three-time CFL all-star and twice named the league's outstanding lineman.
Murphy joined the CFL in 2006 when he signed with the Lions as a free agent.
He signed with the Argos in February 2009.
Prior to joining the CFL, Murphy had stints in the NFL with the Detroit Lions, San Francisco 49ers, Indianapolis Colts, Cincinnati Bengals and Kansas City Chiefs.
"After 13 years of professional football that has spanned four leagues and three countries, I have decided to retire from the Canadian Football League," Murphy said in a release. "The memories and people I have met along the way have equalled the joy I got from physically dominating an opponent on the field."
Murphy plans to discuss his decision more on Thursday at a downtown Toronto bar.
Former Argos coach Jim Barker said Murphy was one of the "great offensive tackles in the league."
"He had a physical presence that made everyone around him better," said Barker. "He was a consummate pro, was always prepared and we were never worried about the left tackle position when he was in the lineup."
Wally Buono, who coached Murphy in Vancouver, said Murphy played a key role in the team's Grey Cup crown.
"His personality, work ethic and toughness were a big part his own success and what made him a great player at his position," said Buono. "The Lions and I wish him the very best."