(CNN) -- There is a new speaker in town.
Rep. John Boehner, R-Ohio, will be the new Speaker of the House of Representatives, replacing Rep. Nancy Pelosi, D-California, as the GOP rolled in Tuesday's midterm elections, gaining a majority for the first time in four years.
The Republican Party will pick up 60 seats or more in the legislature, a statistical analysis of exit polls by CNN projects. That's a comfortable margin over the 39 seats needed to wrest control from the Democrats.
When you lose by 60 in football, it's called a mismatch, and that's what it looked like on Tuesday, as unrest over the economy and government spending, as well as the surge of Tea Party politics helped propel the GOP. And like football players, many Democratic representatives will be walking off the political field slowly after the bruising they suffered.
Tuesday's outcome was comparable to the 1994 so-called "Republican Revolution," when the GOP took 54 seats from the Democrats.
It is also the largest number of House pickups since Democrats picked up 75 seats in 1948.
As of 1 a.m. Wednesday, the Republicans held 225 seats to the Democrats' 150. At least 218 seats are needed for a majority.
"It's clear tonight who the winners really are, and that's the American people," Boehner said Tuesday night in front of a crowd chanting, "Speaker! Speaker!"
The election was a repudiation of big government and politicians who refuse to listen to their constituents, he said.
The message to President Barack Obama was clear, Boehner said: "Change course."
Under a Republican majority, "the people's priorities will be our priorities," an emotional Boehner said.
Obama called Boehner and said he was "looking forward to working with him and the Republicans to find common ground, move the country forward and get things done for the American people," the White House said.
Boehner's camp described the call as "brief but pleasant." The Republican leader told Obama that he's always been straightforward with him in the past, and will continue to be so.
The ramifications of a Republican majority were tempered by the projection that the Senate will remain in Democratic hands. With a Democrat in the White House and a Democratic Senate, both parties will have to reach compromise or risk gridlock in the legislature.
Key Republicans have already hinted that compromise is not a priority on their agenda, as many of them were swept into office precisely because of dissatisfaction with Obama's policies.
The GOP made sizable inroads in Virginia, where a trio of Democratic incumbents were projected to lose, according to CNN analysis of exit poll data. Reps. Tom Perriello, Rick Boucher and Glenn Nye, of the state's 5th, 9th and 2nd congressional districts, respectively, are projected to be out of office.
Republican Robert Hurd won the 5th District, and Morgan Griffith won the 9th District, CNN projected. Republican challenger Scott Rigell won in the 2nd District.
In Florida's 8th District, Democratic Rep. Alan Grayson, a lightening rod for his confrontational and sometimes rude attitude toward his political opponents, lost his seat, CNN projected. Republican Dan Webster, whom Grayson chided as "Taliban Dan" in what many considered an unfair attack ad, will be the area's new congressman.
Two other seats in Florida also switched hands in the Republican's favor. Democratic Rep. Allen Boyd was projected to lose to GOP candidate Steve Southerland. In Florida's 24th district, GOP challenger Sandy Adams will take the place of Rep. Suzanne Kosmas.
With about 100 of the 435 House seats at stake considered "in play," or competitive, an anti-Democratic mood was predicted to result in big Republican gains.
At Democratic Headquarters in Washington, Pelosi gave a brief speech Tuesday as the first polls began to close, thanking the volunteers for their get-out-the-vote efforts, and said that she was going to continue making calls until polls close throughout the country.
"These hundreds of thousands of volunteers are our VIPs," she said. She didn't mention the early results, which were already giving hints of a big day for Republicans.
In Texas, a moderate Democrat, Chet Edwards, who has been a member of the House since 1991, saw his time in Washington come to end. Republican Bill Flores ousted Edwards, who long had represented a conservative district by siding with Republicans on some key votes, including voting against the health care bill.
Other moderate Democrats were able to save their seats. Rep. Heath Shuler, D-North Carolina, was among those in his party who campaigned by running away from it, distancing himself in a debate from Pelosi. He kept his seat Tuesday night, CNN projected.
One moderate Republican wasn't as lucky.
Joseph Cao, a Republican from Louisiana's 2nd district, was the only GOPer to vote in favor of the health care bill. On Tuesday, his constituents elected Democratic challenger Cedric Richmond. That Democratic gain in the state was offset by the projected outcome in the 3rd district, where an open Democratic seat went to Republican Jeff Landry.
Heading into election day, the Democrats had a 255 to 178 advantage in the house, not including two vacancies. Republicans needed to win an additional 39 seats to claim the House majority.
In addition to anti-Democrat sentiments due to a slow economic recovery and what is seen as increased government spending, the advent of the Tea Party movement also played a role in these elections.
The Tea Party has boosted little-known candidates to victory in primaries over mainstream figures across the country. How they fare in the general election will be seen Tuesday. Win or lose, the impact of this group is expected to shift the Republican agenda to the right. That means little chance of compromise or bipartisan approaches on major issues, observers say.
Already, Boehner, has signaled he is not planning to negotiate with the White House or congressional Democrats on his party's top issues.
"This is not a time for compromise, and I can tell you that we will not compromise on our principles," Boehner said last week on Sean Hannity's program.
Recognizing that discontent with Democrats comes from the economic situation and record deficit spending, a priority for the Republicans will be to focus on fiscal issues.
House Republicans have promised to cut $100 billion from the federal budget in the first year, rolling back spending to 2008 levels.
CNN's Dana Bash contributed to this report.