A House vote was expected on the bill within hours as lawmakers raced to wrap up their work for the year.
The measure was a product of a compromise involving Democratic Sens. Charles Schumer and Kirsten Gillibrand of New York and Republican Sen. Tom Coburn of Oklahoma.
The 9/11 legislation provides money for monitoring and treating illnesses related to Ground Zero and reopens a victims' compensation fund for another five years to cover wage and other economic losses of sickened workers and nearby residents. Schumer and Gillibrand had sought $6.2 billion and keeping the compensation fund open for 10 years.
"Every American recognizes the heroism of the 9/11 first responders, but it is not compassionate to help one group while robbing future generation of opportunity," said Coburn, who led a GOP blockade against the bill. "This agreement strikes a fair balance."
The bill gained momentum with help from cable TV personalities. Among the biggest champions of the package were Fox News anchor Shepard Smith and comedian and activist Jon Stewart, who championed the bill and lashed its GOP foes on his Comedy Central TV program "The Daily Show."
The compromise was reached after Democrats scheduled a showdown test vote for Wednesday afternoon and Republicans countered by threatening to run a 30-hour clock before allowing final Senate and House votes on the bill. That would have required keeping both the Senate and House in session for votes on Christmas Eve.
Backers worried that the bill would face a much tougher fight in the new, more fiscally conservative Congress where Republicans will have a stronger hand.
"Any single senator can hold this up way past Christmas and we know that can kill the bill," Schumer said on MSNBC's "Morning Joe" program Wednesday.