He was arrested in Mexico City on 19 March 2009[9] and extradited to the United States in February 2010 to stand trial on narco-trafficking-related charges.

In a 2013 plea bargain deal which was made public by a U.S. District Court in 2014, Zambada admitted to coordinating the smuggling of tons of cocaine and heroin with "El Chapo", Joaquín Guzmán Loera, and agreed to forfeit assets of $1.37 billion to the US government.

"[13][14][15] On 8 November 2018, a plea agreement was filed in the United States District Court for the Northern District of Illinois in which Zambada pleaded guilty to working with El Chapo and others to illegally import thousands of kilos of cocaine into the United States.

Zambada and others used private planes, submarines, and speedboats to smuggle drugs from Colombia to Mexico, and then into the United States.

In return for Zambada's cooperation, the government recommended more lenient sentencing guidelines and that measures be taken to ensure his family's safety.