By a 235-189 vote, largely along party lines, the House sent the bill to the Senate, where it faces longer odds, and defied a veto threat from President Barack Obama.
Passage of the legislation was the most striking victory to date for the 87 freshman Republicans elected last fall on a promise to attack the deficit and reduce the reach of government. Three Republicans joined Democrats in opposing the measure.
"The American people have spoken. They demand that Washington stop its out-of-control spending now, not some time in the future," said freshman Rep. Tim Huelskamp, R-Kan.
The $1.2 trillion bill covers every Cabinet agency through Sept. 30, when the current budget year ends. It imposes severe spending cuts on domestic programs and foreign aid. Targets include schools, nutrition programs, environmental protection, and heating and housing subsidies for the poor.
The measure faces a rough ride in the Democratic-controlled Senate. That was the case even before late GOP amendments pushed the bill further to the right on health care and environmental policy.
Senate Democrats are promising higher spending levels and are poised to defend Obama's health care bill, environmental policies and new efforts to overhaul regulation of the financial services industry.
Changes rammed through the House on Friday and Saturday would shield greenhouse-gas polluters and privately owned colleges from federal regulators; block a plan to clean up the Chesapeake Bay; and bar the government from shutting down mountaintop mines it believes will cause too much water pollution.
In almost every case, the measure sides with business groups over environmental activists and federal regulators.
"This is like a Cliff Notes summary of every issue that the Republicans, the Chamber of Commerce, and the (free market) CATO Institute have pushed for 30 years," said Rep. Edward Markey, D-Mass. "And they're just going to run them through here."
The differences are wide and won't be resolved soon. That confronts lawmakers with the need for a temporary spending bill when the current one expires March 4.
Senate Democrats and House Speaker John Boehner, R-Ohio, are maneuvering for political advantage in anticipation of talks on a short-term extension.
Democrats say Boehner's insistence that any measure carry spending cuts amounts to an ultimatum that could threaten a government shutdown. Such an impasse played to the advantage of Democratic President Bill Clinton in his battles with Republicans in 1995-1996.
The Obama administration upped the ante on Friday, warning that workers who distribute Social Security benefits might face furloughs if the GOP cuts go through.
Across four long days of freewheeling debate, Republicans left their conservative stamp in other ways.
They took several swipes at Obama's year-old health care law, including a vote to ban federal dollars for putting it into effect. At the behest of anti-abortion lawmakers, they called for an end to federal money for Planned Parenthood.
Republicans awarded the Pentagon an increase of less than 2 percent increase, but domestic agencies would endure cuts of about 12 percent. Such reductions would feel almost twice as deep since they would be spread over the final seven months of the budget year.
Republicans back away from some of the most politically difficult cuts to grants to local police and fire departments, special education and economic development. Amtrak supporters repelled an attempt to slash its budget.
About the only victory scored by Obama was on a vote to cancel $450 million for a costly alternative engine for the Pentagon's next-generation F-35 warplane. It was a priority of Defense Secretary Robert Gates and passed with the votes of many GOP conservatives who opposed the $3 billion program.
The Environmental Protection Agency took hits from Republicans eager to defend business and industry from agency rules they say threaten job creation and the economy. The EPA's budget was slashed by almost one-third, and then its regulatory powers were handcuffed in a series of votes.
The measure would block proposed federal regulations on emission of greenhouse gases, which are blamed for climate change. It also would stop a proposed regulation on mercury emissions from cement. Additionally, the bill calls for a halt to proposed regulations affecting Internet service providers and privately-owned colleges.
The 359-page bill was shaped beginning to end by the first-term Republicans, many of them elected with tea party backing.
They rejected an initial draft advanced by the leadership and produced by Rep. Hal Rogers, R-Ky., chairman of the Appropriations Committee, saying it did not cut deeply enough.
The revised bill added more reductions and cut $100 billion from Obama's request for the current year, the amount Republicans had cited in their campaign-season Pledge to America.
But a tea party-backed amendment to cut $22 billion on top of the $60-billion-plus worth of steep cuts already made by the measure failed by almost 2-to-1.
The heavily subsidized ethanol industry absorbed a pair of defeats. One blocks the agency approving boosting the amount of ethanol in most gasoline to 15 percent.
EPA foes prevailed in halting the agency from using its powers to try to curb greenhouse gases. The EPA has taken steps to regulate global warming pollution from vehicles and the largest factories and industrial plants and is expected to soon roll out rules that target refineries and power plants.
The move to stop the EPA from regulating greenhouse-gas polluters came from Rep. Ted Poe, R-Texas, who said his congressional district is home to more oil refineries than any other.