Police in the city of Tempe announced on Friday that 20 people had been arrested and $2.4m was found after a six-month investigation involving local and federal authorities.
Officials said they obtained 15 search warrants and seized an airplane, 14 weapons, 13.6kg of methamphetamine and nearly three tonnes of marijuana.
The Drug Enforcement Administration said the bust was part of "Operation Nayarit Stampede'', aimed at attacking a drug trafficking organisation that stretched across the Mexico border and into Arizona.
The seizure comes after American authorities arrested Noriega Rios, an alleged top operative in the La Familia Cartel, last week.
Noriega was purportedly a contact between the Michoacan Cartel and the powerful leaders of the Sinaloa Cartel, including kingpin Joaquin "El Chapo" Guzman, a man the US Treasury Department has called the world's most powerful drug trafficker.
Officials say the Sinaloa-linked operation sent drugs to New York, Alabama and California, as well as other parts of the country.
The drugs were transported inside hidden compartments of commercial tractor-trailers crossing the Mexican border.
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