Wilson, who finished with 378 yards passing, tallied his fourth consecutive 300-yard passing game while Mellette had more than 100 receiving yards for the 18th time in his career.
Elon led 28-0 at halftime behind three passing touchdowns from Wilson, including two to Mellette, and a 48-yard run from Tracey Coppedge.
Western Carolina rallied in the second half, cutting the deficit to 35-23, but Wilson threw his fifth touchdown of the day, this time a 47-yarder to Mellette, to seal the win.
Eddie Sullivan led Western Carolina with 168 yards on 12-of-22 passing and added 76 yards rushing.
Elon has won the last six games in the series, scoring at least 26 points in each of those meetings.