The Justice Department says Joaquin Guzman Lopez and Ovidio Guzman Lopez were charged in a case unsealed in Washington last week.
Prosecutors allege the two brothers conspired to distribute cocaine, methamphetamine and marijuana in the U.S. for more than a decade.
They are both believed to be living in Mexico and remain fugitives.
Their father was convicted earlier this month on drug and conspiracy charges after a three-month trial in New York. The offenses could put him behind bars for the rest of his life.
His lawyers raised concerns of potential juror misconduct after a juror told Vice News that several members of the panel looked at media coverage of the case.
By MICHAEL BALSAMO ,Associated Press