It set the stage for Thursday, the first full day of tournament that will feature the single biggest mismatch in the history of sports: Victory for Hampton meant a bus ride from Dayton, Ohio, to Louisville, Ky., to meet top-of-the-world Kentucky.
Hampton had a record of 8-14 at one point this season but got hot at the right time and won the Mid-Eastern Athletic tournament championship.
The Pirates were the 24th team with a losing record to make the NCAA tournament, but their win against Manhattan has them at even-par 17-17.
"It's a heck of a reversal for us," Hampton Coach Edward Joyner Jr. said.
But it doesn't make the Pirates half as good as Kentucky, which is 34-0.
Hampton already owns one of the greatest upsets in NCAA tournament history. In 2001, as a No.15 seed, the Pirates shocked No. 2 Iowa State on a Tarvis Williams shot with 6.9 seconds left.
That produced a viral video of then-coach Steve Merfeld running around the court with a crazed, dazed look that hadn't been seen since Jim Valvano took to the floor after North Carolina State miracle-shot its way to the 1983 NCAA championship.
A Hampton win over Kentucky, however, would trump Hampton over Iowa State by a factor of, oh, roughly one billion.
Suggested pep talk: Keep the score to 41-8 at the half, guys, and we will have fared better than UCLA, which was down 41-7.
No building has a high enough roof to contain all the odds stacked against Hampton.
The Pirates entered the tournament without Dwight Meikle, their leading scorer and rebounder, who is out with a high ankle sprain. Then, on Tuesday, Quinton Chievous limped off the court after scoring 15 points in the win over Manhattan.
"I sprained my ankle," Chievous said. "Twice."
Playing Kentucky with two good ankles would have been tough enough.
Since the NCAA tournament expanded to 64 teams in 1985, a No.-16 seeded team never has defeated a No. 1 — in 120 games.
Hampton is not going to be the first.
Reggie Miller, a former NBA player who is now a broadcast analyst, said this week it would take an "act of God" for anyone to defeat Kentucky.
Yet, the Hamptons of college basketball are why we love the opening rounds of the NCAA tournament. This Thursday and Friday are the best two days on the sports calendar.
Hampton's coach played along with the biblical theme following Tuesday's win when a reporter asked: "How big of a mountain do you guys have to climb on Thursday?"
Joyner said he "had Jesus on speed dial."
The coach put his cellphone to his ear and conjured up a conversation. "They want to know how much of mountain and what our odds are," Joyner said. "Hello? Hello?"
A bad connection?
"I guess he'll get back to me," Joyner joked.
Hampton won't have its prayer answered, but maybe the other three lowest bidders can make history against Villanova, Duke or Wisconsin.
Four times a No. 16 has come within four points of victory. Murray State, in 1990, took Michigan State into overtime.
Teams seeded No. 15 haven't fared much better, with a 7-113 record against No. 2.
Still, Arizona, which opens Thursday against Texas Southern, might want to be on alert. In 1993, a second-seeded Wildcats team lost as a 19 1/2-point favorite to a Santa Clara contingent led by Steve Nash.
Texas Southern, coached by Mike Davis, who led Indiana to the 2002 national title game, already has won games at Michigan State and Kansas State.
The Tigers are one reason Portland could be this year's most exciting sub-regional hub. Joining Arizona in Northwest nervousness should be No. 4 Georgetown, which opens against No. 13 Eastern Washington.
Georgetown holds the dubious distinction of being the only program to lose five straight years to schools seeded at least five spots lower. In 2013, the second-seeded Hoyas lost to No. 15 Florida Gulf Coast, which led to USC hiring Andy Enfield.
Another matchup to watch in Portland is No. 12 Stephen F. Austin against No. 4 Utah. Last year as a No. 12, the Lumberjacks upset Virginia Commonwealth.
Truth be told, far more favorites than longshots will survive the next couple of days. It's worth tuning in, though, for the chance at one or two shots in the dark.
Here's to the dreamers who have no idea, in the best way, about what they are facing.
"We're going to go compete," Hampton's coach promised in advance of Kentucky. "We're happy to be here and we're going to fight tooth and nail. You can believe that."