Attorney General Eric Holder said the sweep against networks of the La Familia Michoacana cartel involved more than 3,000 federal, state and local law officers.
U.S. President Barack Obama and Mexican President Felipe Calderon have vowed cooperation to fight the Mexican drug gangs. More than 14,500 people have died in drug-related violence in Mexico since Calderon launched an army-led assault on drug cartels soon after taking office in 2006.
Officials accuse La Familia of shipping large quantities of methamphetamine and cocaine to U.S. cities from Mexico and described its operations as sophisticated and ruthless.
"It is the newest and it is the most violent of the five Mexican drug cartels," Holder said.
"The sheer level and depravity of violence that this cartel has exhibited thus far exceeds what we unfortunately have become accustomed to from the other cartels," he said.
La Familia was different from the other Mexican drug gangs in its use of religion to further its goals and it prohibits members from using illegal drugs, officials said.
"We are fighting an organization whose brutal violence is driven by so-called 'divine justice,'" said Michele Leonhart, acting administrator of the Drug Enforcement Administration.