Sandra Avila Beltran was handed over at the Toluca airport outside Mexico City to U.S. marshals who took her to Miami to face federal cocaine-trafficking charges, the attorney general's office said.
Avila had been acquitted of similar charges in Mexico and her defense argued unsuccessfully that meant she should not be extradited.
In June, a court granted the extradition so she could face the charges pending in the U.S., where prosecutors allege she also had links to cocaine seizures in Chicago. In 2001, U.S. agents intercepted a telephone call in which Avila allegedly asked for payment for 220 pounds (100 kilograms) of cocaine delivered in Chicago.
Federal prosecutors said the extradition request indicates Avila belonged to an organization that trafficked cocaine from Colombia to the United States. U.S. prosecutors allege she helped store and move shipments of the drug from Mexico to the United States.
Until Thursday, Avila had been held in a prison in Mexico's Pacific coast state of Nayarit, pending trial for a separate money-laundering charge. It was not immediately clear how Mexican prosecutors would proceed with that case.
Avila, who was arrested in 2007 sipping coffee in a Mexico City diner, has said she is innocent.
Prosecutors have alleged that Avila spent more than a decade working her way to the top of Mexico's drug trade. They say her romance with Colombian Juan Diego Espinoza brought together Mexico's powerful Sinaloa cartel with Colombia's Norte del Valle.
The Sinaloa cartel led by drug kingpin Joaquin "El Chapo" Guzman has been locked in a vicious fight with the violent Zetas gang in several regions of Mexico.