Another 700 suspects were arrested previously over the course of the DEA's 21-month Operation Xcellerator, officials said.
Attorney General Eric Holder said the cartels "are lucrative, they are violent, and they are operated with stunning planning and precision."
At a press conference announcing the arrests, Holder also suggested that re-instituting a U.S. ban on the sale of assault weapons would help reduce the bloodshed in Mexico, where last year 6,000 people were killed in drug-related violence.
U.S. officials have a responsibility to make sure Mexican police "are not fighting substantial numbers of weapons, or fighting against AK-47's or other similar kinds of weapons that have been flowing to Mexico," Holder said.
DEA Acting Administrator Michele Leonhart said the raid showed the tentacles of the crime syndicate had spread far across the U.S. -- not just to major cities like Washington and Los Angeles, but to quiet, smaller communities like Stowe, Iowa, which the cartel allegedly used as a conduit to funnel drugs around the country.
Leonhart said the Sinaloa cartel has become one of the largest organized crime operations in the world.
The overnight roundup by DEA and state and local police included arrests in California, Minnesota, and the Maryland suburbs of Washington, D.C.
"They've been hit hard, and their ability to spread death and destruction has been diminished" by the arrests, Leonhart said.
Yet while the investigation proceeded over many months, over the same period, the cartel violence on both sides of the border increased substantially.
Kidnappings, killings and other crimes related to the cross-border drug trade have escalated as heavily armed gangs battle for turf on the doorstep of the U.S. narcotics market.
The State Department issued a travel warning on Friday, urging U.S. citizens traveling to Mexico to be aware of the increased threat of violence and kidnapping, especially along the border. The situation in Ciudad Juarez, which lies across the border from El Paso, is of special concern, the State Department cautioned.
It also issued an advisory for the more than 100,000 students who travel to Mexico for spring break. The department warns of the increased border violence and advises revelers to Matamoros and Nuevo Progresso, popular destinations for spring breakers on South Padre Island, Texas, to "exercise common-sense precautions such as visiting only the well-traveled business and tourism areas of border towns during daylight and early-evening hours."