But after years of pleading, months of negotiating, and weeks of just barely edging the contentious bill forward, it suddenly died.
The end was unexpected and dramatic, as McConnell watched Sen. John McCain -- his longtime friend and occasional political rival -- walk to the center of the Senate floor and turn his thumb down to vote "no."
Aides say McConnell knew earlier in the day that McCain's vote was in doubt, and the two men spoke several times about his concerns. But when McCain crossed the floor in front of McConnell to vote, it was still a shock.
McConnell is a conservative, consummate Washington dealmaker who has worked across the aisle for years to painstakingly prevent government shutdowns, raise politically-tricky debt ceilings, and take other steps to keep Washington functioning, even when some in his conference wanted to tear the government down.
At the same time, he can be brutally efficient in service to the Republican agenda, for instance by blocking President Barack Obama's nominee for the Supreme Court, Merrick Garland, last year.
But health care proved to be much tougher than those. The issue divides his caucus so deeply that he was never able to make much tangible progress on bringing together the right flank of his caucus that wanted to get rid of Obamacare's regulations and taxes, and the left flank that wanted to preserve the Medicaid expansion and other protections in the law.
Yet until Thursday night, McConnell could at least keep the process moving with the so-called "skinny bill" and fight for another day.
His face ashen, McConnell stood still and silent for several moments as the magnitude of McCain's vote became clear. The Arizona Republican, who returned to the Senate this week
after a devastating diagnosis of brain cancer to dramatically help advance the health care bill to this vote, became the third and final Republican vote against the health care bill.
A defeated McConnell turned to his caucus and spoke about the loss, admonishing his GOP colleagues who voted no.
"This is clearly a disappointing moment," McConnell said, his voice cracking.
"We told our constituents we would vote that way. When the moment came, most of us did. We kept our commitments," he said. "We worked hard -- and everybody on this side can certainly attest to the fact that we worked really hard -- to try to develop a consensus for a better way forward."
Now Republicans must start over.
McConnell and many of his rank-and-file members said they would not give up on their health care effort. But they have other pressing issues like tax reform, government funding, infrastructure spending -- and another debt ceiling increase to address. Health care might have to wait while tensions ease and Republicans who control the House, Senate and White House rethink their approach.
In a remarkable coda to the night's dramatic events, a few moments after McConnell finished his emotional floor speech, he announced to the chamber that he wanted the Senate to turn next to the annual defense bill and pass it the next day.
McConnell's move -- gesture, really -- was designed to allow the ailing McCain, who chairs the Armed Services Committee, to complete what might be his last defense bill, something he cares deeply about. It is uncertain when he will be in Washington again as he battles his cancer.
However, an objection was heard from Rand Paul, McConnell's fellow GOP senator from Kentucky, who has concerns about military use-of-force authorizations. Procedurally stalled, McConnell adjourned the Senate until Monday, and now it's unclear if McCain will be able to be on hand when his bill comes to the floor.