"We are committed to targeting these new and emerging drugs with every scientific, legislative, and investigative tool at our disposal," Michele M. Leonhart said.
The action netted 5 million packets of finished synthetic drugs and the raw materials that could have been used to create nearly three times that amount. Officials also seized $36 million in cash.
"Today, we struck a huge blow to the synthetic-drug industry," said James Chaparro, an investigations official at ICE.
"The criminal organizations behind the importation, distribution and selling of these synthetic drugs have scant regard for human life in their reckless pursuit of illicit profits."
Poison control centers saw cases related to synthetic drugs more than quadruple between 2010 and 2011, according to the DEA.
Users report experiencing "impaired perception, reduced motor control, disorientation, extreme paranoia, and violent episodes," the agency said, warning that the drugs' long-term effects are "potentially severe."
Sen. Chuck Grassley (R-Iowa) praised the operation and invoked a constituent, David Rozga, who reportedly committed suicide after taking one of the drugs.
"It’s a testament to the cynicism and greed of manufacturers, importers, and distributors that these products were ever put on store shelves," Grassley said.
"If they have any conscience, they’ll find legitimate ways to make money instead of preying on 18-year-olds."