Washington (CNN) -- Veteran Rep. John Boehner of Ohio became the 61st speaker of the House of Representatives Wednesday as Republicans officially took charge of the chamber for the first time in four years and dramatically changed Washington's political landscape.
Democrats maintained control of the Senate for the new 112th Congress, but with a reduced majority.
The change likely presages a stark ideological conflict with President Barack Obama, who is preparing to defend his legislative accomplishments of the past two years and position himself for a re-election campaign in 2012.
Ninety-four new House members were sworn in Wednesday, along with 13 new senators. The new House has the largest freshman class with no previous experience in elective office since 1948.
Republicans now hold a 242-193 majority in the House. Democrats hold at 53-47 majority in the Senate.
Boehner, first elected to the House in 1990, inherited the speaker's gavel from Rep. Nancy Pelosi, D-California. Boehner's rise to the top position caps a remarkable political comeback. He was voted out of the House leadership in 1998 after Republicans unexpectedly lost seats to Democrats that year.
Ten of Boehner's 11 siblings were present when he was formally sworn in by Michigan Rep. John Dingell, the longest-serving member of the House.
"Hard work and tough decisions will be required of the 112th Congress. No longer can we fall short," Boehner said after taking the gavel. "No longer can we kick the can down the road. The people voted to end business as usual, and today we begin carrying out their instructions."
He promised minority Democrats "an honest debate" and "a fair and open process."
"There's a great deal of scar tissue that's been built up on both sides of the aisle," he said. But "we can disagree without being disagreeable."
Pelosi, before handing over the gavel, reiterated that House Democrats are prepared to work with the Republicans on proposals to help the middle class, create jobs, and cut the deficit.
"We extend the hand of friendship," she said. "But where we cannot find common ground, we must stand our ground."
She also appeared to predict a quick Democratic resurgence, promising that "two years from now when we come together, things will be different."
The first order of business for the new House majority was passage of a new set of rules to govern the chamber. In a nod to GOP freshmen with ties to the conservative Tea Party, all new legislation will be required to include a "Constitutional Authority Statement," specifying which section of the Constitution allows for passage of the bill.
The Constitution will be read aloud on the House floor on Thursday.
The Republican majority also will require any spending increase to be offset by a spending cut of a similar size. New spending will not be allowed to be funded by tax increases.
Every bill will have to posted online for 72 hours before a final vote.
Also in the GOP's crosshairs is Obama's health care overhaul, widely considered to be the president's signature domestic accomplishment.
Republicans unveiled legislation to repeal the measure Monday night. They plan a key procedural vote on Friday and a final vote the following Wednesday, according to House GOP sources.
Democrats are dismissing the plan as little more than a hollow nod to the GOP's conservative base. Most political analysts say that while a repeal of the measure can pass the new Republican House, it has no chance of surviving the Democratic-controlled Senate or overcoming a presidential veto.
Connecticut Rep. Rosa DeLauro, addressing reporters at a news conference with other House Democratic leaders Tuesday, called the GOP move "disingenuous" and "nothing but political theater."
"It is a Kabuki dance," she said. "The fact of the matter is we're not going to repeal health care. It is not going to happen."
Three members of Obama's Cabinet -- Treasury Secretary Tim Geithner, Labor Secretary Hilda Solis, and Health and Human Services Secretary Kathleen Sebelius -- released a letter to members of Congress Wednesday warning that a reversal of the overhaul would be economically devastating.
A repeal would lead to "higher costs and skyrocketing premiums, less competition, and fewer consumer protections against industry abuses," they wrote.
In keeping with the GOP's pledge to reduce the size of government, one of the first votes in the Republican House will be to cut the chamber's operating budget by 5%. Republican aides claim the move will save $25 million.
Boehner has promised House Republicans will roll back federal spending to 2008 levels, and has pledged to hold weekly votes on spending cuts. Republican leaders have refused to offer specific proposals, however, for cuts to major entitlement programs such as Social Security, Medicare, and Medicaid. They have also promised not to cut national security spending or veterans' benefits.
Together, these programs comprise the bulk of the federal budget.
In their "Pledge to America" released during last fall's campaign, House Republicans said that restoring spending to "pre-stimulus, pre-bailout" levels would translate to at least $100 billion in cuts within one year. House GOP aides are now backing off that pledge, however, arguing that the calculation was based on Obama's proposed budget, which was never enacted.
They are now estimating that the cuts will add up to between $50 billion and $60 billion.
Also certain to cause partisan friction: a vote to raise the federal debt ceiling, which is likely to come this spring.
The ceiling -- a cap set by Congress on the amount of debt the federal government can legally owe -- is currently set at nearly $14.3 trillion. The ceiling is expected be reached within a few months. Conservatives have expressed strong opposition to raising the ceiling, but a failure to do so could trigger a major financial crisis.
CNN's Dana Bash, Deirdre Walsh, Richard Greene and Ed Hornick contributed to this report