The panel recommended US regulators approve the daily pill, Truvada, for use by people considered at high risk of contracting the Aids virus.
The US Food and Drug Administration (FDA) is not required to follow the panel's advice, but it usually does.
Some health workers and groups active in the HIV community have opposed the approval of the drug.
However, correspondents say the move could prove to be a new milestone in the fight against HIV/Aids.
Truvada is already approved by the FDA for people who are HIV-positive, and is taken along with existing anti-retroviral drugs.
Studies from 2010 showed that Truvada, made by California-based Gilead Sciences, reduced the risk of HIV in healthy gay men - and among HIV-negative heterosexual partners of people who are HIV-positive - by between 44% and 73%.
The Antiviral Drugs Advisory Committee, which advises the FDA, voted 19-3 in favour of prescribing the drug to the highest risk group - non-infected men who have sex with multiple male partners.
They also approved it, by majority votes, for uninfected people with HIV-positive partners and for other groups considered at risk of acquiring HIV through sexual activity.
The votes followed an 11-hour meeting of the panel in Silver Spring, Maryland, and a lengthy public comments session.
Opposition to the prospect of approving the drug is based on concerns that users could gain a false sense of security, and fears of a drug-resistant strain of HIV.
There is also concern that the high cost of Truvada could divert limited funding from more cost-effective options.
"We need to slow down. I care too much about my community not to speak my concerns," said Joey Terrill, of the Aids Healthcare Foundation, which campaigned against the drug's approval.
Nurse Karen Haughey told the panel: "Truvada needs to be taken every day, 100% of the time, and my experience as a registered nurse tells me that won't happen.
"In my eight years, not one patient that I've cared for has been 100% adherent."
But others welcomed the panel's recommendation.
"This brings us closer to a watershed for global HIV prevention efforts," said Mitchell Warren, executive director of the Aids Vaccine Advocacy Coalition, after the vote.
The FDA is expected to make its decision by 15 June.