The Republican-led committee voted 14-13 along party lines with Democrats having accused Kennedy over two days of contentious confirmation hearings of being financially vested in the anti-vaccine movement and peddling conspiracy theories to sow doubt about lifesaving medicines - assertions Kennedy rejected.
If confirmed in the full Senate, he will run the US Department of Health and Human Services, which oversees more than $US3 trillion ($A4.8 trillion) in healthcare spending, including agencies such as the Food and Drug Administration and the agency in charge of Medicare and Medicaid health programs that provide health insurance for about 140 million people in the US.
Kennedy has faced opposition from health groups, Democrats, family members and the Wall Street Journal and New York Post editorial boards, who say he is unfit for the job because of his role in the anti-vaccine movement.
Kennedy has long sown doubts about the safety and efficacy of vaccines that have helped curb disease and prevent deaths for decades.
He disputes the anti-vaccine characterisation and has said he would not prevent people in the US from getting inoculations.
Shares of vaccine manufacturers and packaged food companies fell after the vote.
Pfizer's stock was down 1.8 per cent, along with US shares of its COVID-19 vaccine partner BioNTech, which was down 3 per cent.
Moderna was down 5.1 per cent and Novavax down about 1 per cent.
Shares of Hershey, Mondelez, Kraft Heinz , General Mills were all down 2 per cent.
Kennedy calls for banning hundreds of food additives and chemicals.
He has called for getting ultra-processed foods out of school lunches.
Before the vote on Tuesday, Republican committee member Bill Cassidy - a medical doctor who also chairs the Health, Education, Labor and Pensions Committee - was seen as a potential swing vote against Kennedy after he said during a confirmation hearing last week that he was struggling with the decision.
As the vote was occurring, Cassidy posted on social media platform X that he had "very intense conversations" with Kennedy and the White House over the weekend and Tuesday morning.
"I want to thank VP JD (Vice President JD Vance) specifically for his honest counsel," Cassidy added.
"With the serious commitments I've received from the administration and the opportunity to make progress on the issues we agree on like healthy foods and a pro-American agenda, I will vote yes."
Kennedy now needs the support of at least 50 senators, which would allow Vance to cast a tie-breaking vote to confirm his nomination.
The Republican-controlled Senate has not rejected any of Trump's nominees so far.
His defence secretary pick Pete Hegseth squeaked by in a 51-50 vote after Vance was needed to break a tie in January.
The Senate Intelligence Committee is due on Tuesday to vote behind closed doors on former US representative Tulsi Gabbard's nomination to become director of national intelligence, another Trump nominee facing an uncertain path to confirmation.
