Sims rushed for a career-high 207 yards, including touchdown runs of 72 and 52 yards, and Houston continued its best start in school history with a 73-17 victory on Thursday night that matched a season-high in points.
"He's a special, really talented player and just a lot of fun to watch," Keenum said of Sims. "It's nice to have him in the backfield right there next to me."
Keenum passed for 325 yards, a pedestrian total by his standards, before he was given the rest of the night off in the third quarter. His three touchdown passed went for 66, 23 and 8 yards to Patrick Edwards, who also scored on a 70-yard punt return.
Houston (10-0, 6-0 Conference USA), which came in averaging 52.7 points per game, was held without a point in the first quarter, snapping a streak of 19 straight quarters with a score.
The Cougars responded with five touchdowns in the second quarter, beginning with Bryce Beall's 11-yard scoring run that was set up by Sims' 56-yard scamper.
"After the first quarter, we were able to run the ball and mix up some passes pretty well," Keenum said. "Just a good game plan, good coaching. ... It's just execution. When we are executing and not making mental mistakes, silly mistakes, we're able to roll."
Orleans Darkwa rushed for 123 yards and two touchdowns for Tulane (2-9, 1-6).
Sims, the Conference USA freshman of the year in 2009, missed all of 2010 with what Houston said was a retroactive transcript matter with the NCAA. He returned this season as part of a three-man running back rotation with Beall and Michael Hayes, and came into the game second on the squad in rushing with 451 yards.
Sims' longest run through the first nine games was 50 yards, which he surpassed three times in the second quarter alone in helping Houston take a 35-10 halftime lead despite the fact that Keenum had passed for only one TD to that point.
"We just needed someone to step up and make plays," Sims said. "It felt real good just to get down field and start scoring."
Keenum, who last week became the NCAA's all-time leading passer, increased his career total 17,537 yards.
He threw for his final two TDs in the third quarter and was given the rest of the night off with Houston leading 52-10. Keenum finished 22-of-29 passing and kept alive his streak of more than 300 yards passing in every game this season.
It was also the 35th 300-yard game of Keenum's career, which ranks second in NCAA history, right behind the 36 of former Hawaii quarterback Timmy Chang.
Keenum now needs only 49 yards passing to become only the second player in NCAA history -- along with Chang -- to have three 4,000-yard seasons. Houston still has two more regular season games, and a bowl game, in which Keenum could potentially become the first NCAA player ever to have three 5,000-yard seasons.
Keenum's departure did not end the Houston onslaught, as backup quarterback Cotton Turner led two scoring drives, which included his 27-yard scoring pass and his 35-yard touchdown scramble.
Tulane interim coach Mark Hutson said the Green Wave's defense made plenty of mistakes, but would have had trouble slowing down Houston's passing game no matter what.
"Their receivers -- I watched the instant replay -- they made some unbelievable catches," Hutson said.
Damian Payne added a 76-yard punt return for a score, which was Houston's second touchdown on a punt return in the game.
Houston might have set a new season high score if coach Kevin Sumlin hadn't ordered the Cougars to run out the clock on their last offensive series, drawing groans from traveling fans wearing red behind Houston's bench.
"When you get beat 73-17, you are embarrassed, you are humiliated, you are disappointed, you are frustrated," Hutson said. "But we have two games left to take the bitterness and the disappointment out. We need to go to Houston on (Nov. 19) and play well against Rice."
Taking it all in from a suite in the Superdome was former Michigan and West Virginia coach Rich Rodriguez, the offensive coordinator at Tulane under Tommy Bowden in 1998, when the Green Wave went 12-0.
Rodriguez saw firsthand how much work he'd have to do should he decide to return to head coaching at Tulane.
The Green Wave opened the game with a nearly seven-minute drive that covered 66 yards in 15 plays, including three conversions on third down and another on fourth-and-short, only to come up empty when Ryan Griffin was intercepted by Phillip Steward on an underthrown ball in the end zone.
Tulane got as close as 14-7 in the second quarter, when Darkwa muscled into the end zone from 3 yards out, one play after he had been caught from behind on a 66-yard run.
However, it took only four plays before Houston was back up by two TDs on Sims' 52-yard scoring run.