He's now jumped to second place in the race for delegates, giving front runner Mitt Romney a wakeup call.
The former Pennsylvania senator picked up big wins in Minnesota, Missouri and Colorado, shaking up the Republican race for president.
Romney on Wednesday tried to put a positive spin on the surprising results.
"No such thing as a coronation in presidential politics, it's meant to be a long process," he said.
Santorum's sweep was a major blow to Romney's efforts to wrap up the nomination.
"The gift of being underestimated is a wonderful gift," a reinvigorated Santorum said. "I think you may have seen a little bit of that last night."
Even before the results were in last night, the Romney camp was trying to downplay expectations.
"Mitt Romney is not going to win every contest," his political director wrote in a memo to reporters, "but unlike the other candidates, our campaign has the resources and organization to keep winning over the long run".
Romney admitted that his campaign didn't take advantage of that.
"Sen. Santorum was able in Minnesota to level a lot of charges, some of them not accurate, and I wasn't there to respond," Romney said.
Santorum's huge night was also a blow to Newt Gingrich. The former House speaker is trying to hold onto his spot as the conservative alternative to Romney.
The high point of Ron Paul's night was a second place finish in Minnesota. He's now focusing his attention on the next contest in Maine, where he and Romney are the undisputed favorites.
Romney is still the frontrunner to win the GOP nomination, but now a more damaged one.
Santorum's surge appears to be boosting his fundraising.
He has collected $400,000 in the past couple of days, including $250,000 since his wins Tuesday night.
Santorum is now ahead of Gingrich in second place in the competition for Republican National Convention delegates.
The Associated Press contributed to this report.