The USDA said it discovered four tissue samples that tested positive for the virus using its swine surveillance program.
The sample was collected in late October, and the USDA said the pigs as well as the people caring for the animals have recovered.
Last month, tests confirmed that several show pigs at the Minnesota State Fair contracted the H1N1 virus.
The USDA declined to say where in Indiana the sick pigs were located.
USDA officials have stressed repeatedly that instances of pigs with H1N1 flu do not pose a threat to consumers of pork products.
Still, word of a commercial herd contracting the virus for the first time is bad news for the pork industry, which has struggled with poor prices blamed on swine flu fears and the global recession.
Agriculture experts expected that H1N1 virus would eventually show up in domestic swine and a vaccine for hogs is being developed but not yet available. News of the virus in pigs came after herd infections in several other countries, including Canada, Australia, Argentina, Ireland, the United Kingdom and Norway.
The positive tests in Indiana came just days after U.S. officials successfully negotiated an end to one of the more damaging commercial effects of the flu — a six-month ban on pork imports to China. Officials expect the Chinese to reopen their import markets, offering pork producers an opportunity to export to what was their fastest growing market before the H1N1 outbreak.