In doing so, FDU became the second 16-seed in tournament history to advance into the second round, joining the 2018 UMBC Retrievers.
Adding to the unlikeliness of their upset, the Knights are the shortest team in all of division one basketball this season – among 363 teams – and they had to deal with seven-foot-four National Player of the Year candidate Zach Edey.
Edey still had his way, scoring 21 points on seven-of-11 shooting while adding 15 rebounds and three blocks. He became the first player in tournament history to put up those numbers and still lose, dating back to when blocks became an official stat in 1986.
It was the only shocking upset of the day, although the six-seed Iowa State Cyclones were totally outmatched in their 59-41 defeat at the hands of the 11-seed Pittsburgh Panthers.
Despite a quiet game from the top NBA prospect in action Friday – Keyonte George – the three-seed Baylor Bears had no issue sending home the UC Santa Barbara Gauchos 74-56.
George, a six-foot-four freshman guard, is averaging 15.8 points, 4.2 rebounds and 2.8 assists as a starter on a quality outfit, but he had just nine points against the Gauchos as the Baylor starters got an early rest.
The most eye-catching individual performance of the day came from reigning National Player of the Year Oscar Tshiebwe, with the six-foot-nine senior piling up 25 rebounds in the six-seed Kentucky Wildcats' 61-53 triumph over the 11-seed Providence Friars.
Tshiebwe finished with 11 offensive rebounds to go with 14 on the defensive end, adding eight points, three steals and two blocks.
The other top seeds in action all survived and advanced, with two-seed Marquette beating 15-seed Vermont 78-61, three-seed Gonzaga getting the better of Grand Canyon 82-70, and three-seed Xavier surviving an early scare to overcome Kennesaw State 72-67.
FDU became just the second 16-seed ever to advance at the NCAA Tournament with Friday's sensational 63-58 win.
Purdue had won the regular season title and the Big Ten Tournament this year, but Anderson was confident his underdogs could cause an upset.
Indeed, following the Knights' win in their play-in game, Anderson told the team: "The more I watch Purdue, the more I think we can beat them. Let's go shock the world."
FDU did exactly that, with the coach gushing in his latest post-game message to his players – while he also outlined a desire to keep this fairytale run going.
"We outplayed them for 40 minutes, we were the better team for 40 minutes," Anderson said.
"Our style was tremendous. We played how we had to, we played how we had to play. Unbelievable team effort, unbelievable approach.
"Listen, you just made history boys. You just made friggin' history, college basketball history tonight. After four wins last year, this whole team together... it is one of the most unbelievable stories of all – and that's all on you guys.
"Listen, we're playing pretty damn well now. Hydrate, do all the stuff we have to do, and we can do something even more.
"Hey, we are going to enjoy this, and I am so proud of you. What an unbelievable, special moment for the rest of our lives."
This will go down as perhaps the biggest upset in March Madness history, yet it also felt painfully familiar for Purdue.
The Boilermakers lost to 15-seed Saint Peter's last year, becoming the first team to lose consecutive NCAA Tournament games against 15-seeds or worse – excluding the First Four.
Purdue coach Matt Painter acknowledged his team would have to "sit in it", adding: "There's nothing you can say that's going to change it, right?
"I mean, it stinks. They outplayed us. They out-coached us. I think that's the one thing as a coach that you always face, and you'll get ridiculed. You'll get shamed, you'll get whatever.
"It's basketball. You've got to get better. You've got to keep fighting to get yourself in this position and then be better. And that's what we have to do."
Boilermakers center Zach Edey had been one of the most dominant players in college basketball this year, averaging 22.3 points, 12.9 rebounds and 2.1 blocks, but his 21 points, 15 rebounds and three blocks were not enough.
There will be discussion now around Edey's future amid doubts about his suitability to the NBA, with Painter saying his "level-headed" star would "take the information in and make a decision and do what's best for him".
The coach added: "He's a good dude. It's too bad. He deserves better than this. He deserves better."
The Peacocks thrived off a home-court advantage at the Wells Fargo Center to become the first 15th seed to reach the Elite Eight, despite the late efforts of NBA lottery prospect Jaden Ivey.
Despite hitting on none of his opening five attempts from the perimeter, Ivey connected on an NBA-range triple with eight seconds left to bring Purdue within a point. Doug Edert calmly made his free-throws to ice the game, and put Saint Peter's on the brink of the Final Four.
They will face North Carolina who defeated UCLA 73-66, led by 30 points from Caleb Love.
Despite shooting 10-of-31 from the three-point line for the night, the six-time national champions overcame a three-point deficit to put up 45 points in the second half.
Elsewhere, Remy Martin scored a season-high 23 points as Kansas hung on for a 66-61 win over Providence, securing their passage to the Elite Eight.
The Jayhawks are the only first seed left in the tournament, after both Gonzaga and Arizona were defeated in the Sweet 16 on Thursday, and Baylor's title defence was ended in the second round.
Kansas will face the Miami Hurricanes, who progressed with their comfortable 70-56 win over Iowa State.
