Collins announced her opposition to the Graham Cassidy Health Care Bill on Twitter about two hours after Hatch's Senate Finance Committee completed contentious hearings on the measure.
Graham Cassidy was hanging by a thread. Kentucky's Rand Paul and John McCain of Arizona were already opposed, and Republicans could not afford another defection.
As disability advocates shouted from the Committee Room and the hallway, Hatch tried to open the meeting.
"If you can't be in order then get the heck out of here," Hatch said as he pounded the gavel.
Soon the door closed, and Senators spent more than five hours questioning the bill's sponsor and a group of health care experts.
Graham Cassidy would take money spent on Medicaid and Obamacare and distribute it to states to create their own health systems.
Late in the day, the Congressional Budget Office issued a preliminary analysis of the legislation, saying millions of Americans would lose their health insurance if it became law. Collins announced her decision shortly after the report.