NFL Network's Ian Rapoport and Mike Garafolo reported an initial MRI showed Murphy tore his ACL.
ESPN's Adam Schefter added Murphy also tore his MCL, in addition to his ACL.
The injury occurred in the first quarter when Murphy was involved in a third-down stop against the Ravens offense. He was helped off the field by members of Washington's medical staff and didn't speak to the media after the game.
Murphy was going to start the regular season suspended for the first four games after violating the NFL's policy on performance-enhancing drugs. The 26-year-old recorded a career-high nine sacks in 2016, trailing only Ryan Kerrigan's 11 among Washington defenders.
Since being drafted by Washington in the second round in 2014, Murphy has only missed one game in his career. Preston Smith is the team's starter at outside linebacker, with Lynden Trail likely to see more playing time with Murphy out for the season.