Washington (CNN) -- Voters gave control of the House of Representatives to Republicans in midterm elections, sending a message of discontent to Washington two years after Barack Obama's historic win.
Rep. John Boehner, a Republican from Ohio, is expected to be the new House speaker. He will replace Rep. Nancy Pelosi, a Democrat from California, as the GOP gained a majority for the first time in four years.
"The American people spoke, and I think it's pretty clear the Obama-Pelosi agenda is being rejected by the American people," Boehner told reporters on Wednesday. "They want -- as I said last night, they want the president to change course, and I think it's change course we will."
"We're humbled by the trust that the American people have placed in us, and as I said last night, our job is to listen to the American people and follow the will of the American people."
He said Americans "want us to do something about cutting spending here in Washington and helping to create an environment where we'll get jobs back in our country, so we've got a big job ahead of us -- and that's why you'll see us roll up our sleeves and go to work today."
The Republican Party will pick up the more than 39 seats needed to wrest control from the Democrats, according to a CNN analysis of exit poll data.
By early Wednesday, Republicans held 239 seats to the Democrats' 183 -- well over the 218 seats needed for a majority, according to CNN projections.
Tuesday night, before a crowd chanting "Speaker! Speaker!" Boehner said, "it's clear tonight who the winners are and that's the American people."
The election was a repudiation of big government and politicians who don't listen to their constituents, he said. Under a Republican majority, "the people's priorities will be our priorities," Boehner said.
Obama, who was swept into office in 2008 amid a message of hope and inclusiveness, 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."
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.
The election 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.
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 legislative gridlock.
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, andMorgan 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 lightning rod for his confrontational 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.
With about 100 of the 435 House seats at stake considered "in play," or competitive, an anti-Democratic mood has been predicted to result in big Republican gains.
Pelosi defended Democrats in a statement early Wednesday.
"Over the last four years, the Democratic Majority in the House took courageous action on behalf of America's middle class to create jobs and save the country from the worst economic catastrophe since the Great Depression," she said.
She urged lawmakers to help move the nation forward.
"We must all strive to find common ground to support the middle class, create jobs, reduce the deficit and move our nation forward."
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 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 distanced himself from Pelosi. He kept his seat Tuesday night, CNN projected.
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.
The Tea Party has boosted little-known candidates to victory in primaries over mainstream figures across the country. Win or lose, the 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.
Key Republicans, including Boehner, have hinted that compromise is not a priority on their agenda, as many were swept into office due to dissatisfaction with Obama's policies.
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 and Mariano Castillo contributed to this report.