Smith amassed 323 yards and added a rushing touchdown for the Mountaineers (1-0), who blitzed the Thundering Herd for 655 total yards.
Paul Millard threw a touchdown pass while Shawne Alston rushed for 123 yards and two touchdowns on 16 carries in West Virginia's first win as a member of the Big 12 Conference.
WVU's Stedman Bailey made nine grabs for 104 yards and two scores.
Marshall (0-1) was led by Rakeem Cato, who completed 38-of-54 passes for 413 yards, two touchdowns and an interception.
Celebrity Breakups and divorces of 2014 [PHOTOS]