The tea party conservative stopped speaking at 12 noon EDT Wednesday, sitting down to yield the floor.
The Texas freshman began talking Tuesday afternoon, seeking the urge defunding of the 3-year-old health system overhaul. Fellow conservatives helped by making occasional remarks.
Cruz had virtually no chance of prevailing.
The Senate debated the House bill defunding the health care law while preventing a government shutdown on Tuesday.
Cruz wanted to derail it because Senate Democrats have the votes to remove the health care provision before sending the bill back to the House.
Many Republicans opposed Cruz's effort, fearing their party might be blamed if the government closes.