The Eagles found themselves trailing 14-6 to start the final quarter after playing through heavy snowfall during much of the contest.
But McCoy then found his footing, scoring on runs of 40 and 57 yards en route to club record for rushing yards in a single game.
Quarterback Nick Foles capped the rally with a 1-yard scoring plunge following a seven-play, 71-yard drive as the NFC East-leading Eagles (8-5) secured a fifth straight win.
Foles completed 11-of-22 passes for 179 yards and a touchdown with an interception.
Jeremy Ross returned a kickoff 98 yards for a score for NFC North-leading Detroit (7-6), which fell for the third time in four games.
Matthew Stafford was limited to 10-of-25 through the air for 148 yards.