Emma Coronel Aispuro, 31, a regular attendee at her husband's trial two years ago, was arrested at Dulles International Airport in northern Virginia, and is expected to appear in a federal court in Washington on Tuesday.
Coronel was charged in a one-count complaint with conspiring to distribute heroin, cocaine, marijuana and methamphetamines for unlawful importation into the United States, the Justice Department said.
A lawyer for Coronel could not immediately be identified.
Guzman was convicted in February 2019 of trafficking tons of drugs and engaging in multiple murder conspiracies as a top leader of the Sinaloa Cartel, one of Mexico's largest, most violent drug trafficking organisations. (Reuters)