"The inside of my ankle has collapsed," Johnson told reporters.
Johnson came into the campaign carrying an ankle injury. He was frequently listed on the weekly injury report but ended up playing in seven of the Eagles' first 10 games. He also suffered an MCL sprain in Week 7.
However, the 30-year-old University of Oklahoma product no longer being able to play through the pain is a major loss to the Philadelphia offensive line.
Johnson started 99 games across eight years since the Eagles selected him with the fourth overall pick in the 2013 NFL draft. He'd received a modest 71.2 overall grade from Pro Football Focus this season while trying to compete through the injuries.
His season-ending injury presents yet another problem for the team's offensive line, which was already facing changes.
John Clark of NBC Sports Philadelphia reported Friday the team will shift Jordan Mailata to left tackle with Jason Peters moving to right guard. Matt Pryor could move from right guard out to tackle to replace Johnson. Jack Driscoll and Brett Toth are the team's reserve options at the position.
The Eagles' offensive line alterations come ahead of a tough six-game stretch to finish the regular season, which kicks off Monday night against the Seattle Seahawks.
Philadelphia currently sits second in the NFC East with a 3-6-1 record, a half-game behind the Washington Football Team (4-7) for the division lead.