The pill, called Atripla, includes three medicines approved by the US Food and Drug Administration (FDA) that already form one of the most widely prescribed treatments for HIV and Aids and was approved by the FDA on Wednesday.
The medicine is expensive: A month's supply costs more than $1,000.
However, the drug can replace the two or more pills HIV-positive patients now must take each day to keep the virus in check, making it simpler to stick to a treatment regimen, the manufacturers say.
Andrew von Eschenbach, the FDA's acting commissioner, said having a single pill would provide an opportunity to "significantly improve compliance", adding that "compliance with therapy is as important as the therapy itself for a successful outcome".
If the single pill does help patients stick to their pill-taking regimen, that in turn could slow the emergence - and ultimately, transmission - of drug-resistant strains of the virus, the manufacturers say.
Those strains can evolve when patients take less than 95% of their pills, said John Martin, head of Gilead Sciences, the manufacturer of two of the drugs in Atripla.
"The idea of having a fixed-dose combination has been one of the ... holy grails"
FDA deputy commissioner
"The fewer pills, the better they are able to achieve that 95% threshold," he said.
However, Atripla will not do away with the multiple other drugs that Aids patients often must take to fend off infections and other complications of their weakened immune systems, said Frank Oldham Jr, executive director of the National Association of People with Aids.
Some patients will also have to take other HIV drugs along with Atripla to combat the virus effectively.
Atripla will also be made available for use in the 15 countries covered by US Aids programmes.
Interest in Atripla may be greatest in developing countries, for both medical and logistical reasons, said Murray Lumpkin, deputy commissioner for international and special programmes at the FDA.
"The idea of having a fixed-dose combination has been one of the ... holy grails," Lumpkin said.
About 40 million people worldwide, including one million Americans, are HIV positive. Each year, roughly five million people are infected with HIV and three million die from Aids, according to the World Health Organisation.