Zambada is one of the most consequential traffickers in Mexico's history and co-founded the Sinaloa Cartel with El Chapo, who was extradited to the United States in 2017 and is serving a life sentence in a maximum-security prison.
Both Zambada and Joaquin Guzman Lopez, the son of El Chapo, face multiple charges in the US for funnelling huge quantities of drugs to US streets, including fentanyl, which has surged to become the leading cause of death for Americans between the ages of 18 and 45.
Zambada, who is believed to be in his 70s, and Guzman Lopez, who is in his 30s, were detained after landing in a private plane in the El Paso area, two US officials told Reuters.
Guzman Lopez is one of four sons of El Chapo - known as Los Chapitos, or Little Chapos - who inherited their father's faction of the Sinaloa Cartel.
Attorney General Merrick B. Garland Statement on Arrests of Alleged Leaders of the Sinaloa Cartel Ismael Zambada Garcia (El Mayo) and Joaquin Guzman Lopez— U.S. Department of Justice (@TheJusticeDept) 🔗: https://t.co/LumvDMKx2F pic.twitter.com/Wcm20MLrhCJuly 26, 2024
His brother, Ovidio Guzman, was arrested in 2023 and extradited to the United States.
In recent years, the Sinaloa Cartel has become the biggest target for US authorities, who have accused the crime syndicate of being the biggest supplier of fentanyl to the United States.
Zambada and Guzman Lopez face multiple charges in the US "for heading the cartel's criminal operations, including its deadly fentanyl manufacturing and trafficking networks", US Attorney General Merrick Garland said in a statement.
US authorities had a $US15 million ($A23 million) reward for Zambada's capture, while Guzman Lopez had a $US5 million bounty on his head.
The Sinaloa cartel traffics drugs to more than 50 countries and is one of two most powerful organized crime groups in Mexico, according to US authorities.
Zambada and El Chapo's sons belong to two different generations of traffickers, with differing styles.
Zambada is known for being an "old school" narco, avoiding the limelight and operating in the shadows.
Sinaloa cartel co-founder Joaquin "El Chapo" Guzman is serving a life sentence in a US prison. (AP PHOTO)
El Chapo's sons, by contrast, have a reputation for being flashy narcos who courted attention as they ascended the ranks of the cartel.
El Chapo's sons are also known to be more violent and hot-headed than Zambada, who had a reputation as a shrewd operator.
Zambada and El Chapo's sons have had a fractious relationship since their father was extradited in 2017, and the arrests of Zambada and Guzman Lopez may trigger instability or even violence in their heartlands in the northern state of Sinaloa.
Previous arrests of important cartel leaders has triggered violence as power vacuums open, leading to significant infighting within the organisations and between them and their rivals.
Their arrests were part of a joint operation by the FBI and Homeland Security Investigations.
US authorities have in the past year launched fresh indictments against Zambada and Guzman's sons on new charges in the United States that focus on fentanyl smuggling, as well as the flow of precursor chemicals to the illicit labs operated by their crime syndicate.
Over decades, the cartel has set up sophisticated supply chains to move drugs across the globe and to source heavily regulated chemicals to their home base in Sinaloa.
