The Mountaineers (1-1) scored on six of their first seven drives with little resistance and got the production from their running game that was missing in a season-opening loss to Alabama.
Trickett followed up a solid performance last week by completing 35 of 40 passes for 348 yards before being replaced by freshman William Crest late in the third quarter.
In the first meeting between the schools, Towson (0-2) of the Championship Subdivision couldn't keep up with West Virginia's up-tempo spread offense. The Mountaineers ran 96 offensive plays and amassed 606 total yards.
West Virginia posted its first shutout since beating Coastal Carolina 31-0 in the 2010 season opener.
The Mountaineers also scored more points than in any game last year.
Trickett had plenty of help. Four teammates had rushing touchdowns and 11 different receivers had catches, led by Kevin White with 10 receptions for 101 yards.
West Virginia's Rushel Shell showed he's capable both with his feet and hands, following a 16-yard run with an 18-yard reception on a screen pass in the third quarter. Shell had a game-high 71 rushing yards and had four receptions for 47 yards.
Trickett completed 13 straight passes at one point. Right after the streak was snapped, Trickett's 19-yard scoring toss to Jordan Thompson early in the third quarter put the Mountaineers ahead 38-0.
Later in the quarter, Trickett threw a short pass that Cody Clay caught near the ground in the end zone on fourth down. It was initially ruled a touchdown but was overturned on review and the Mountaineers turned the ball over on downs.
West Virginia got some of those points back with a safety on the next play when Towson's Connor Frazier was called for intentional grounding in the end zone.
Frazier couldn't shake the constant pressure of the defense in his second career start. Towson got past midfield twice and was limited to 122 total yards.
West Virginia's only trouble on offense came on finishing drives early in the game.
It needed three rushing plays from inside the Towson 5 on the opening series before Wendell Smallwood's 1-yard TD. With a first-and-goal from the 2 on West Virginia's next series, Shell was stuffed for a 2-yard loss from the 1 on third down and the Mountaineers settled for a short field goal, while Josh Lambert missed a 34-yard try on the third series.
West Virginia got clicking in the second quarter when Mario Alford converted a 6-yard reception on third down inside the 5 to set up Shell's 2-yard scoring run.
Later, Trickett's short lofted pass to Alford initially was ruled incomplete before the officiating crew got together and ruled it a touchdown. On West Virginia's next series, Trickett scored on a 5-yard run for a 31-0 halftime lead.