The Congressional Budget Office estimated the revised measure would lower deficits by $132 billion over a decade, with the possibility of much higher reductions in the subsequent decade.
Forecasters said the bill would expand coverage to roughly 94 percent of eligible Americans under age 65, a total that excludes illegal immigrants.
Majority Leader Harry Reid of Nevada said the measure "will finally level the playing field between American families and the insurance industry."
With Nelson's decision, Obama's Senate allies appear on track to pass the legislation by Christmas, overcoming unanimous Republican opposition and a swirling early winter snowstorm.
"This bill is a legislative train wreck of historic proportions," Senate Republican leader Mitch McConnell of Kentucky said. He said it includes cuts to Medicare, home health care and hospices as well as "massive tax increases" at a time of double-digit unemployment.
At its core, the measure is designed to spread coverage to tens of millions who lack it, while banning insurance company practices such as denial of coverage on the basis of pre-existing medical conditions. The White House also wants the legislation that eventually makes it through Congress to slow the rate of growth in national medical spending overall. The House passed its version of the legislation last month, and final compromise talks are expected quickly.
Nelson disclosed his decision as Majority Leader Harry Reid, D-Nev., unveiled a final series of changes designed to solidify support. Among them was an increase in the Medicare payroll tax of 0.9 percent on income over $200,000 a year for individuals and $250,000 for couples. The bill earlier raised those taxes by 0.5 percent.
The legislation includes new limits designed to limit insurance company profits and overhead, by requiring them to spend 80 percent of their premium income on medical care for individual insurance policies, and 85 percent for group policies. The industry says such a limitation is unnecessary because profits generally are in the single digits.
The estimated 30 million Americans purchasing coverage through new insurance exchanges would have the option of signing up for national plans overseen by the same office that manages health coverage for federal employees and members of Congress. Those plans would be privately owned, but operated on a nonprofit basis, as many Blue Cross Blue Shield plans are now.
The option amounts to a consolation prize for liberals, who failed to include a government-run alternative.
Additionally, insurance companies would be barred immediately from denying coverage to children because of a pre-existing health condition. The prohibition on denial of coverage for adults would not take effect in the Senate bill until 2014, a disappointment for consumer advocates.
On abortion, the measure would let a state disallow coverage in new insurance exchanges by passing a law to that effect. Additionally, it sets up a mechanism to segregate funds that would be used to pay for abortions from federal subsidy dollars flowing to health plans.
Federal law now prohibits public money for abortions, except in cases of rape, incest or to save the life of the mother. From the beginning, the issue has been how those restrictions would be applied to a new stream of federal money under the overhaul bill.
The developments occurred as Republicans dug in to delay the inevitable for as long as possible. They objected when Reid sought permission for Nelson to announce his decision in a speech on the Senate floor, then forced Senate clerks to spend hours reading aloud the text of the 383-page package of changes.
Republican opposition, coupled with Senate rules requiring 60 votes to overcome a filibuster, gave Nelson enormous leverage as he pressed for concessions that included stronger restrictions on abortions to be covered by insurance policies offered in a newly overhauled health care system.