The Senate approved an $854 billion measure Thursday that funds much of the government, including $675 billion for the Defense Department.
The bill combines military spending with disbursements for Health and Human Services, Education, Labor and other agencies.
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The bill was approved, 85-7, and now heads to the House.
With the vote, the Senate has passed nine of the 12 mandatory spending bills for the budget year that begins Oct. 1. That's a marked departure from recent years, when individual spending measures were routinely ignored in favor of giant spending packages that fund the entire government.
The Senate had not passed a labor/health spending bill in more than a decade.
The bill boosts military pay by 2.6 percent and the National Institutes of Health by 5 percent.
Republicans cited defense spending in urging support for the measure, which accounts for about two-thirds of federal spending for the 2019 budget year. The 2.6 percent military pay raise is the largest in nearly a decade.
The 5 percent boost for NIH is the fourth straight significant increase for the biomedical research agency. The measure would hike spending for Alzheimer's research to more than $2.3 billion, essentially quadrupling spending levels from four years ago on a disease that requires hundreds of billions of dollars for dementia-related care.
Republican Sen. Roy Blunt of Missouri, chairman of the Appropriations subcommittee on labor and health, said that if the United States does not find a solution to the disease by 2050, "we will be spending about twice today's defense budget on Alzheimer's care."
The bill also would provide a $145 million increase for treatment of opioid addiction, bringing spending to $3.7 billion to confront what lawmakers called an epidemic of abuse.
It would also boost spending for the Head Start preschool program and increase maximum Pell Grants for college education.
Sen. Richard Shelby, R-Ala., chairman of the Senate Appropriations Committee, said the vote "shows what the Senate can do working together. We all know it's not easy, but it works."
Some conservatives criticized Republicans for going along with Democratic demands for increases in non-defense spending that match the increase in defense spending. The Heritage Foundation, a conservative think tank, said the bill "continues to fund wasteful and ineffective programs that should be curtailed or eliminated entirely" and omits several policy riders important to conservatives.
Senate leaders from both parties have agreed to avoid attaching so-called poison pill proposals to spending legislation to ensure passage.
The Senate rejected an amendment sponsored by Kentucky Sen. Rand Paul to block taxpayer dollars from going to Planned Parenthood and other groups that perform abortions. Paul said the amendment offered Republicans who "profess pro-life values" a chance "to turn our words into action, stand up for the sanctity of life and speak out for the most innocent among us that have no voice."
Only 45 senators voted in favor of the proposal.
Senate leaders also blocked an amendment by Sen. Joe Manchin, D-W.Va., that would have allowed the Senate to intervene in a Texas lawsuit that could upend health-care protections for people with pre-existing medical conditions. The Trump administration has said it will no longer defend key parts of the Obama-era Affordable Care Act in court.
"What's happening today in the Senate is disgusting," Manchin said after the amendment was blocked. He said Senate Majority Leader Mitch McConnell "chose to play politics with the health care of millions of Americans," including about 1.8 million people with pre-existing conditions in McConnell's home state of Kentucky.
"This is not a Democratic or Republican issue, this is life or death to many," Manchin said.
Manchin's election opponent, West Virginia Attorney General Patrick Morrissey, has joined states challenging the health care law.
The House has approved a $675 billion spending bill for the Defense Department, but has not voted on a spending measure for labor, health and education. Senators from both parties have said they want to keep the two measures attached.
Associated Press writer Kevin Freking contributed to this story.