The eight, all of Indian origin and living in New York City or suburbs, were arrested Thursday morning, the Justice Department said.
The opioids were mislabelled in India to hide their illegal nature and sent over here to be mailed by the defendants to customers in the US, the department said.
It did not identify those who allegedly sent the drugs from India.
"The defendants participated in a black market for prescription medications by distributing millions of opioid pills in tens of thousands of transactions in one year alone," federal prosecutor Richard Donoghue said.
The epidemic of opioids has become a national crisis with 47,600 deaths from overdoses in 2017, according to government statistics.
Those arrested and charged with conspiracy in connection with drug distribution were Ezhil Sezhian Kamaldoss, Harpreet Singh, Parthiban Narayanasamy, Baljeet Singh, Deepak Manchanda, Gulab Gulab, Mukul Chugh and Vikas M. Verma.
Kamaldoss also faces money laundering charges.
According to the Justice Department, distributors in India shipped misbranded Tramadol, a synthetic opioid, and other drugs to individuals and entities in the US using the postal system and commercial couriers.
The eight people arrested operated out of a warehouse in the Queens district of New York City where they repackaged the pills and mailed out millions of pills to customers across the country, the department said.
In their operations, they maintained daily ledgers detailing the names, addresses, pill size and pill amounts ordered by customers, according to the department.
During the course of the investigation that began in January 2018, they distributed millions of Tramadol pills, the department said.
Mark McCormack, the Special Agent-in-Charge of the Food and Drug Administration, said that the illegal distribution of opioids was fueling the national national crisis.
(Arul Louis can be contacted at arul.l@.in and followed on Twitter @arulouis)
( With inputs from IANS )