Rothfus is a suburban Pittsburgh attorney who won a narrow victory in a 12th Congressional District redrawn by the Republican-controlled Legislature to push its boundaries toward the outskirts of Pittsburgh.
Critz has been fighting to keep his seat since winning the special election in 2010 after his former boss, longtime Democratic Rep. John Murtha, died in office.
Rothfus was able to flip the seat in one of the most closely-watched races in the country. The campaign has been flooded with $9.9 million in spending by outside groups, more than any other House race in the nation.
Rothfus said early Wednesday morning he was tired but after a long, tough campaign but looking forward to getting to Washington.
"We had the right message in southwestern Pennsylvania," he said in a phone interview. "We're very concerned about the direction of the country."
Rothfus' win helped Republicans pick up a seat in Pennsylvania, meaning the GOP will have 13 of the state's 18 U.S. House seats in January.
In eastern Pennsylvania, Republican Rep. Mike Fitzpatrick fended off a strong challenge from Democratic attorney Kathy Boockvar.
Most incumbents on the ballot otherwise easily won re-election. Republican Reps. Tom Marino, Bill Shuster and Tim Murphy were among those securing another term in Washington, joining victorious Democrats including Reps. Bob Brady, Chaka Fattah and Allyson Schwartz.
Also in eastern Pennsylvania, the seat once held by longtime U.S. Rep. Tim Holden is staying in Democratic hands after attorney Matt Cartwright defeated Republican Laureen Cummings, a nurse and small business owner.
Cartwright defeated Holden in the Democratic primary in April in the 17th Congressional District. Holden was first elected to Congress in 1992 as a conservative, so-called Blue Dog Democrat.
The 4th District in central Pennsylvania will stay in Republican control after Scott Perry, a GOP state representative and colonel in the Pennsylvania Army National Guard defeated Democrat Harry Perkinson, an engineer. Incumbent GOP Rep. Todd Platts is retiring.
Critz's seat was most endangered, especially after the Republican-controlled Legislature redrew congressional district boundaries to account for population shifts in the 2010 census. Democratic critics said the new congressional district map was gerrymandered to give the GOP an edge.
Critz's new district the blue-collar power base of Johnstown established by Murtha, but stretched to new ground north and east of Pittsburgh.
Democrats have a slight edge in voter registration in the new district, though the area traditionally votes Republican.
"We almost overcame nearly insurmountable odds. We gave them a run until the very end," Critz told a disappointed crowd in Johnstown, including Murtha's widow, Joyce. Critz also enjoyed the endorsement of former President Bill Clinton, who remains popular in western Pennsylvania.
It apparently wasn't enough to hold off Rothfus. Critz pledged his full cooperation in the transition.
Rothfus, a corporate attorney, supports free trade and repealing the health care reform package pushed by President Obama. He said Tuesday night his first priority when he arrived in Washington in January was to make sure small businesses weren't burdened with impending tax increases.
A graduate of Notre Dame law school and a cancer survivor, Rothfus has run two marathons.
This is his first win in a general election. He lost to former U.S. Rep. Jason Altmire in 2010. Altmire was defeated in the Democratic primary by Critz earlier this year.