Forty-nine people are facing criminal charges over their involvement in a scheme to steal Red Cross funds meant for the victims of Hurricane Katrina.
Call centres were set up to speed delivery of aid to hurricane victims
Many of those indicted worked at a Red Cross call centre in California and are accused of helping family and friends make false claims for relief money.
The FBI was brought in to investigate after the Red Cross noticed an unusual number of payments made in the area.
An estimated $500,000 (£291,000) was stolen through the scheme.
The US justice department says the number of people charged could rise.
None of those indicted worked directly for the American Red Cross, officials said, but had been employed by subcontractors to staff the call centres.
The Red Cross' Bakersfield call centre was the largest of three set up to process hurricane relief claims as quickly as possible in the wake of Katrina.
Investigators allege that 22 workers employed there abused the system by helping family and friends to make false claims for aid money, giving them instructions on who to call and what to say about their situation.
The false claimants were ultimately given a pin number they could use to claim the funds from Western Union.
None of the group charged lived along the Gulf Coast or were affected in any way by the hurricane, says the BBC's Daniela Relph in Washington.
The Red Cross accepts that post-Katrina the pressure to get the money out to those in need meant the safeguards in place were not fully adequate, our correspondent adds.
It is now working with the FBI to ensure such fraud is easier to detect in future.
In a statement, the Red Cross said it did everything possible to seek out and prosecute fraud.
Instances of fraud represent only a small percentage of the overall contributions made to the organisation, it said.
The American Red Cross has faced questions in the past over its handling of large emergency relief schemes, notably the Liberty Fund set up in the wake of the 11 September 2001 attacks.