Various media projections indicate Republicans will pick up at least 50 seats -- some project 60 seats -- in the House. They needed 39 seats to retake the lower chamber.
The 2010 midterm elections were not the races in which the incumbency was powerful. Veteran Democrats such as Rep. John Spratt of North Carolina, chairman of the House Budget Committee, and Ike Skelton of Missouri, leader of the House Armed Services Committee, both were defeated.
U.S. House Speaker-apparent John Boehner, R-Ohio, pledged the new House majority would listen to the electorate that elevated them to power.
"Let me just say this: It's clear tonight who the real winners are -- and that's the American people," Boehner said. "The American people's voice was heard at the ballot box."
With high unemployment, crushing debt and national lawmakers held in such low esteem, "This is not a time for celebration," Boehner said, saying Election Day put Washington on notice.
"For far too long Washington's been doing what's best for Washington and not for the American people," Boehner said, "tonight that begins to change."
CNN reported that President Barack Obama spoke with Boehner and was trying to reach out to House Speaker Nancy Pelosi.
In the Senate, Majority Leader Harry Reid won a tough re-election battle against Republican challenger Sharron Angle.
"Today, Nevadans chose hope over fear. Today Nevadans chose to move forward, not backwards," Reid told supporters. "You made possible what many thought was impossible."
Democrats won a key race in California, with incumbent Democratic Sen. Barbara Boxer fending off a challenge from former Hewlett-Packard chief Carly Fiorina.
But in the midst of Democrats' big wins, there were some big losses as well, projections indicated.
U.S. Rep. Mark Kirk, R-Ill., was projected to take over President Barack Obama's former U.S. Senate seat, media outlets indicated.
Eighteen-year veteran U.S. Sen. Russ Feingold of Wisconsin lost his seat to Republican challenger businessman Ron Johnson, results show.
Sen. Blanche Lincoln, D-Ark., who ran into opposition from liberals in the Democratic primary, lost to Republican John Boozman.
Tea Party-backed Republican candidate Rand Paul won the U.S. Senate race in Kentucky, defeating Democrat Jack Conway for the seat vacated by retiring Jim Bunning.
"I have a message from the people of Kentucky ... a message that is loud and clear and does not mince words," Paul said in his victory speech. "We've come to take our government back."
Marco Rubio was the winner in the three-candidate race for Florida's U.S. Senate seat over Democrat Kendrick Meek and independent Charlie Crist, the outgoing governor.
Rubio said GOP wins across the country don't mean voters approve of the Republican Party.
"It would be a grave mistake to view this as an embracing of the Republican Party," Rubio said. "It's a second chance ... to be what they said they would be so long ago."
In Delaware, Democrat Chris Coons defeated Christine O'Donnell, the Tea Party-supported Republican candidate in the race for the seat once held by Vice President Joe Biden.
The seat held by the late Sen. Robert Byrd, D-W.Va., will remain in Democratic hands, as popular Gov. Joe Manchin defeated GOP businessman John Raese.
In a nod to the influence of the Tea Party movement in this year's elections, South Carolina Sen. Jim DeMint, chairman of the conservative caucus, told CNN the results indicated "an awakening going on in our country."
While not committing to founding a Senate Tea Party caucus similar to one in the House of Representatives, DeMint said, "if there is one, I'll join it."
Two gubernatorial races made history Tuesday, with South Carolinians electing the first Indian-American female governor and New Mexico electing the first Latina commander in chief.
In South Carolina, Nikki Haley, a businesswoman whose parents are immigrants from India, will be the first Indian-American female governor, defeating Democrat Vincent Sheheen in a tight race.
Republican Susana Martinez of New Mexico became the first female Hispanic governor in America, defeating her Democratic opponent, Lt. Gov. Diane Denish.
In budget-strapped California where two-term Republican Gov. Arnold Schwarzenegger couldn't run again, results indicated former e-Bay chief Republican Meg Whitman spent $140 million of her personal fortune to lose to Democratic Attorney General Jerry Brown, who would be the state's governor for a third term. He served his first two terms from 1975 to 1983.