As Kennedy was sworn into the post on Thursday, US President Donald Trump signed an executive order to establish a commission to "Make America Healthy Again", that would investigate chronic illness and deliver an action plan to fight childhood diseases.
Kennedy said his first priorities would be around "radical transparency" and removing those in the government who had conflicts of interest.
"For 20 years, I've gotten up every morning on my knees and prayed that God would put me in a position where I could end the childhood chronic disease epidemic in this country. On August 23 of last year, God sent me President Trump," Kennedy said, referring to when he dropped his independent presidential bid and endorsed the Republican candidate.
The US Senate earlier on Thursday voted to confirm Kennedy 52-48, with Senator Mitch McConnell the lone Republican joining all 47 Democrats to vote against Kennedy, who had made pledges to protect existing vaccination programs in a bid to secure votes of hesitant lawmakers.
Kennedy will now oversee multiple high-profile agencies, including the FDA and Centers for Disease Control and Prevention.
Kennedy, 71, is an environmental lawyer who has long sown doubts about the safety and efficacy of vaccines that have helped curb disease and prevented millions of deaths for decades.
He will now run an HHS department that directs more than $US3 trillion ($A4.8 trillion) in healthcare spending. Also under HHS purview are the Medicare and Medicaid programs that provide health insurance for over 140 million Americans and the National Institutes of Health.
In addition to pledging to work to end chronic disease, Kennedy has said he wants to break any ties between employees at the US drugs regulator and industry. Opponents argued that he is unfit for the job because of his prominent role in the anti-vaccine movement.
Kennedy's path to confirmation was fraught and did not always appear to have the necessary votes among Republicans.
He had to overcome his past as a life-long Democrat, his previous views in support of abortion, as well as his stance on vaccines. Some prominent members of his own family, including cousin Caroline Kennedy, also urged his rejection.
Ultimately, Senate Republicans closed ranks as they have for every Trump cabinet selection so far.
The Trump White House has said it plans to drastically shrink the size of the federal government. Kennedy has said he wants to get rid of many employees at both the FDA and NIH.
Democrats 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 he rejected.
with AP
