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 swine flu, also known as 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 swine 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 swine flu 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 swine 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 swine flu outbreak.
Separately Wednesday, officials said that the virus has been confirmed in a cat treated at the Iowa State University College of Veterinary Medicine.
It's the first known case of the virus to be diagnosed in a cat. Veterinarians say the virus has also been confirmed in two ferrets.
The 13-year-old cat was treated and is recovering.
The veterinarian who treated the cat, Dr. Brett Sponseller, says two of the three people in the same house had flu-like symptoms before the cat became ill.
The case was confirmed at both Iowa State and the U.S. Department of Agriculture.
Sponseller says the flu is known to spread from humans to pets, but this is the first case of swine flu to spread to a cat.