Taken daily or weekly, the pill would allow couples to share the burden of family planning.
The study shows that the small molecule makes male mice reversibly infertile without putting a damper on their sex drive.
"Our findings demonstrate that, when given to rodents, this compound produces a rapid and reversible decrease in sperm count and mobility with profound effects on fertility," said Dana-Farbe's James Bradner, the study senior author.
Importantly, the results of early experiments suggest the effects would be temporary, with fertility quickly rebounding on stopping taking the pill.
"This compound produces a rapid and reversible decrease in sperm count and motility with profound effects on fertility," said Bradner.
"A male birth control pill hasn't been easy to come by in large part because of the challenge of getting any drug across the blood-testis barrier, where it can reach the sperm generating cells," scientists said.
The lack of contraceptive alternatives for men is partially responsible for the high rate of unplanned pregnancies, they said.
The new drug, which is known only as JQ1, disrupts a crucial stage of sperm development. It is hormone-free, and in tests on mice, it did not produce any side-effects.
When mice are given the BRDT-inhibiting molecule, they begin producing fewer sperm and those sperm they do produce don't swim as well.
Sperm production plummeted and what sperm were made were bad swimmers, the journal Cell reported. The animals were still interested in sex but, when the dose of the drug was right, were unable to sire any pups.
However, when they were taken off the drug, their fertility quickly returned and they became father to normal-sized, healthy, litters.
Also in JQ1's favour is the fact it could be given in pill-form. Most male contraceptives in development are jabs or patches.
"There has not been a new reversible contraceptive for men since the development of the condom, centuries ago," said William Bremner from the University of Washington.
