It was the first time since the 2009-10 season that the Mountaineers won a conference game by as large of a margin.
It was also the first time WVU has scored 100 or more against a ranked team since it scored 111 against Wake Forest in the 2005 NCAA tournament.
WVU defeated a top 25 team by its biggest margin of victory since 1998.
"We really understand that we need every game," said WVU point guard Juwan Staten. "We feel like we can score with any team.
It was West Virginia's first win over an opponent rated as high as No. 11 since Jan. 7, 2012 when the Mountaineers defeated No. 9 Georgetown. WVU is 2-1 against top 25 teams in its last three chances after losing 16 straight prior to the team's 91-86 victory over then-No. 21 Oklahoma on Feb. 5.
It was the best win in terms of RPI ranking since March 2, 2011 in a win against No. 6 Connecticut.
West Virginia (15-10, 7-5) recorded its best RPI win since 2011 in a win against No. 6 Connecticut. Iowa State (18-5, 6-5) came into the game with the No. 7 RPI in the country according to statsheet.com.
"I don't lie to them," said WVU head coach Bob Huggins about his team's NCAA tournament chances. "The worst thing that could happen that they would say to me, ‘I wish you would've told us.' If I was them, I'd want to know what I'd have to do.
"It's a marathon, not a sprint. It's a long year."
WVU, which had trouble keeping a lead against many teams this year, found a way to convincingly defeat a team with as close to a complete game as it has played.
The Mountaineers were led by Staten who finished with nearly a triple-double. He had 19 points, nine assists and seven rebounds.
"We feel like we've gotten so much better as a team as the season has went along," Staten said. "We're growing up."
Junior forward Remi Dibo scored a career-high 20 points after hitting six threes before fouling out with 1:49 to play.
"My teammates did a great job of finding me, and I did a good job of knocking down those shots," Dibo said.
Fellow sophomore guard Eron Harris finished with 16 points before leaving the game after picking up a flagrant two foul late in the contest.
"They're all good wins. We just want to focus on winning game after game after game," Harris said. "At the end of the day, that's all it is - winning the next game."
WVU shot 53.8 percent for the game and held the Cyclones to 36.6 percent shooting. West Virginia also made 13-of-22 threes. Iowa State was just 4-of-23 from beyond the arc.
ISU was led by forward Georges Niang, who had 17 points. He fouled out with 8:08 to play. Forward Melvin Ejim, coming off his 48-point performance in his last game, finished with six points though he did have 12 rebounds.
Iowa State Deandre Kane seemed affected by the boisterous WVU student section and Staten's defense. Kane had 14 points but added five turnovers.
"We didn't want them to make threes. When you look at when they've played really well, they've made a bunch of threes. We wanted to take the three ball away from them," Huggins said.
After trailing by four early on, the Mountaineers went on a 9-0 run – two threes from Henderson and another from freshman forward Nathan Adrian – to take a 13-8 lead into the first timeout of the game.
The Mountaineers took a 20-14 advantage on a nifty drive and layup to force a timeout from the Cyclones.
West Virginia would take its first double-digit lead of the game at 25-14 with more than nine minutes to play in the first half.
That lead would grow to 16 points on a nifty layup from Staten, but a three from Niang cut the Mountaineers' lead back to 13. ISU had missed its first seven 3-pointers before that make.
WVU would go on a 14-6 run to end the first half including a demonstrative drive and layup through three defenders from Staten to take a 52-33 advantage into the break.
The Cyclones, who hadn't lost a game by more than 11 points all season long, were down by 19 after just 20 minutes to the Mountaineers, which had perhaps their best half of the year. In the half, WVU shot 50 percent from the field and 54 percent from 3-point range. Three players – Harris, Henderson and Staten had at least nine points – at this point in the game.
Iowa State was 1-of-12 from three in the first half and shot just 38.2 percent from the field.
Iowa State would cut the Mountaineers' lead to just 14 early in the second half due to some strong play from Niang. However, WVU would take its biggest lead of the game up to that point by going on a 12-2 run to take a 71-46 lead.
"Our talk at halftime was about how we couldn't let up," Staten said. "We just came out, we didn't change our game plan ... and we just continued to play defense."
West Virginia would really cruise to victory from that point on, as WVU students started an "overrated" cheer with more than 10 minutes left in the game.
Iowa State held a 44-to-34 rebound advantage, but the Mountaineers had the advantage in turnovers with six fewer than the Cyclones.
WVU's junior forward Kevin Noreen finished with eight points and three rebounds in one of his best games of the season. Adrian scored nine points before fouling out with 4:24 to play.
"That's the best Nate's played," Huggins said. "He made three defensive plays when it was cut to a 15-point lead in the second half that really changed the game … that's what I'm used to seeing guys do. I thought he was really good."