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 $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 bill also blocks money for President Barack Obama's health care law. It is on its way to the Democratic-controlled Senate, where it faces tough opposition. The president is also threatening a veto.
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.
Meantime, many states are struggling with their own budgets - most notably in Wisconsin, where thousands of workers are protesting.
The Associated Press contributed to this report.