Darby injured his right knee on a non-contact play during the third quarter of Sunday night's 27-20 loss to the Cowboys. The 24-year-old was seen wearing a brace on his knee in the locker room.
The loss of Darby is a significant one for the Eagles (4-5), who are getting thin in the secondary. Fellow cornerbacks Jalen Mills (foot) and Sidney Jones (hamstring) sat out Sunday night's game with injuries.
Rasul Douglas started for Mills versus Dallas, while free safety Avonte Maddox moved into the nickel position for Jones. Undrafted rookie Chandon Sullivan, who spent time on the practice squad, replaced Darby at cornerback on Sunday night.
Considered the Eagles' top cornerback, Darby will join starting free safety Rodney McLeod (torn MCL) on injured reserve.
Darby recorded 43 tackles, 12 pass breakups and an interception in nine games this season.
He was acquired by the Eagles in a trade with the Buffalo Bills in 2017.
Darby has collected 214 tackles and six interceptions in 46 career games with the Eagles and Bills. Buffalo selected Darby in the second round of the 2015 NFL Draft.