Morris Claiborne's 99-yard kickoff return circuited a West Virginia comeback attempt, spurring No. 2 LSU to a 21 victory over the 16th-ranked Mountaineers.
Jarrett Lee threw for 180 yards and touchdowns to Odell Beckham, Rueben Randle and Chase Clement for the Tigers (4-0), who scored 20 unanswered points to end the game.
Michael Ford posted 82 yards and two rushing scores on 12 carries, and Spencer Ware added 92 yards on the ground.
Geno Smith completed 38-of-65 passes for 463 yards, two touchdowns and two interceptions for West Virginia (3-1), which hadn't lost at home since last October 23 against Syracuse.
"They have very good athletes, and they outplayed us and outcoached us," WVU head coach Dana Holgorsen said.
Stedman Bailey and Tyler Urban were the beneficiaries of Smith TD passes, while Dustin Garrison posted a rushing score in defeat. Tavon Austin led all receivers with 187 yards on 11 receptions.
LSU's Drew Aleman missed a 30-yard attempt wide right, then West Virginia climbed within 27-14 on its first possession of the second half. A six-play, 80-yard drive culminated in a 12-yard Smith-to-Urban connection.
The Mountaineers then got within six points as Garrison took it in from the one to put the exclamation point on a 90-yard march, but Claiborne fielded the kickoff at his own one-yard line and didn't stop until he reached the end zone to give LSU more breathing room at 34-21.
Smith's pass on 4th-and-3 from the LSU 43 fell incomplete, and Ford's 15-yard touchdown run with 9:55 remaining gave the Tigers a 40-21 edge after the conversion pass fell incomplete.
Smith followed by coughing up the ball at the Tigers' 43, and Alfred Blue's 18-yard TD run capped the scoring with 3:03 to go.
"We showed up tonight in a very hostile environment. ... We showed up tonight in a very hostile environment," LSU head coach Les Miles said.
LSU struck on its opening possession as Lee found Randle for an 11-yard score.
Later in the first, Smith was picked off by Brandon Taylor and the Tigers set up at midfield. Seven plays later, Ford broke off a 22-yard run to paydirt, but the extra point was missed and it was 13-0.
West Virginia got on the board with 2 1/2 minutes gone in the second, when Smith hit Bailey, who eluded a tackler and rolled along the left sideline for a 20-yard score.
But LSU picked up two more TDs before the end of the half, as Lee found Beckham for a 52-yard connection and Clement for a one-yard score.
LSU extended its nation-leading regular season non-conference win streak to 36, dating back to a 26-8 loss in the 2002 season opener at Virginia Tech...The Tigers' 27 first-half points were the most in any half against a ranked team on the road since scoring 28 points -- all in the fourth quarter -- at No. 15 Arizona State on Sept. 10, 2005...LSU took a 20-14 decision in Baton Rouge last year...West Virginia won the offensive battle, racking up 533 yards to 366 for the visitors...Bailey finished with 115 yards on eight catches...Beckham had two grabs for 82 yards.