Despite Cruz' effort, a test vote was set for Wednesday. Reid had filed a motion to proceed to the measure, and under Senate rules lawmakers will vote even if Cruz speaks for hours and keeps the Senate in session overnight.
The Cruz filibuster, which began at 2:41 p.m., echoed the effort of Sen. Rand Paul, R-Ky., who in March waged a nearly 13-hour filibuster of John Brennan's nomination for CIA director over the president's authority to use drones in the United States. The Senate eventually confirmed Brennan.
Outside conservative groups that have been targeting Republican incumbents implored their members to call lawmakers and demand that they stand with Cruz and his attack on Obamacare.
"This is the ultimate betrayal," the Senate Conservatives Fund said of McConnell and Cornyn — two lawmakers up for re-election next year — in an email Tuesday morning. They pressed their members to "melt the phones," arguing that "we can't let these turncoats force millions of Americans into this liberal train wreck."
The Club for Growth and the Madison Project also pressed lawmakers to back Cruz' effort.
The issue has roiled the Republican Party, exacerbating the divide between tea party conservatives and GOP incumbents who repeatedly have voted against the health care law but now find themselves on the defensive. Republican senators said defunding Obamacare simply won't happen with a Democratic president and Democrats controlling the Senate.
"It will be a cold day in Gila Bend, Ariz., before we defund Obamacare," said Sen. John McCain, R-Ariz., the party's 2008 presidential nominee. "A very cold day. In fact there may be a snowstorm. ... I know how this movie ends. I don't know all the scenes before it ends, but I know how it ends. We don't defund Obamacare."
Sen. Saxby Chambliss, R-Ga., said that as long as Obama has the power to veto legislation, "the fate of that bill is pretty much in his control, and we know what he's going to do."
Associated Press writers Andrew Taylor, Alan Fram, David Espo and Laurie Kellman contributed to this report.
- Here's a quiz to test your Star Wars...
- 5 faith facts about Ben Carson: retired...
- Britain's new princess can't expect...
- The Latest on prophet cartoon case: 1 man's...
- Report highlights earth-shattering increases...
- Defeated boxer Pacquiao keeps faith, as do...
- LA man builds small home for homeless lady
- Defending the Faith: Going up to Jerusalem
- Rage to relief in Baltimore as 6... 40
- Former tech executive Carly Fiorina... 19
- 5 faith facts about Ben Carson: retired... 18
- More Americans spending at least half... 15
- Governor, legislators leave 'baggage'... 14
- Famed neurosurgeon Ben Carson announces... 11
- Latest on police-custody death: 53... 9
- Clinton agrees to testify on Benghazi,... 9