His arrest was not linked to the 5,000-per cent increase in the price of Daraprim, a drug used to treat malaria and infections suffered by HIV-positive individuals.
The FBI said he was targeted instead in an embezzlement probe at another company he once led, Retrophin.
Also arrested was Evan Greebel, a lawyer who was outside counsel to Retrophin, the agency said.
Shkreli, a 32-year-old former hedge fund manager, gained notoriety in September when his company, Turing Pharmaceuticals, raised the price of Daraprim from USD 13.50 a tablet to USD 750 after acquiring the drug.
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"Price gouging like this in the specialty drug market is outrageous," Democratic frontrunner Hillary Clinton said on Twitter, vowing to fight runaway drug prices.
Turing later announced that while it would not lower the drug's per tablet price, it would negotiate agreements with health groups on wholesale prices.
Shkreli specializes in buying patents on inexpensive drugs and then hiking their price.
In November, he gained control of another drug company, Kalobios Pharmaceuticals, whose stock price plummeted Tuesday on news of his arrest, falling 53.24 per cent to USD 11.03 before trading was suspended.