The freshman Texas Republican said he would speak against implementation of the healthcare reform law passed by Congress and signed into law in 2010 "until I am no longer able to stand," The Washington Post reported.
"I rise today in opposition to Obamacare," Cruz said. "A great many Texans, a great many Americans, feel they do not have a voice, and so I hope to play some very small role in providing the voice."
The Post noted the longest filibuster in U.S. history was a 24-hour, 18-minute effort by the late Sen. Strom Thurmond and other southern senators opposed to civil rights laws. The newspaper said Senate rules now in place mean Cruz will have to yield the floor by Wednesday afternoon at the latest.
Cruz said Sen. Mike Le, R-Utah, would join him.
U.S. Senate Minority Leader Mitch McConnell, R-Ky., said political heat should be focused on Democrats during the debate over the budget and healthcare reform.
McConnell told reporters Tuesday Senate Democrats are putting their political popularity on the line by opposing a House-passed budget bill that would strip funding for Obamacare, officially known as the Affordable Care Act.
"We are giving them a do-over -- a second chance," McConnell said. "Will they double-down on this failed experiment ... or join us in taking it off the books?"
McConnell -- who said Monday he would not support a filibuster against the spending bill -- is the latest GOP leader to declare the healthcare reform law a failure even before it has gone into effect. The Republican-led House of Representatives passed a measure that would authorize continued funding of the government, but no money to implement healthcare reform.
Democrats accuse Republicans of pursuing an "ideological agenda" on the issue.
The Hill said Senate Republicans were scolding the leadership for risking a government shutdown over Obamacare, but it appeared Tuesday the Democrats had enough votes to pass the spending measure in time without the defunding provision.
Contingency planning was under way Tuesday in the event the spending measure failed and the government was indeed shut down after current spending authorization expires Monday. Roll Call said much of the municipal spending in the District of Columbia requires congressional approval and the city was considering emergency legislation that would keep city workers on the job in the event of a shutdown.