The agency said it targeted individuals from across the country, in what it called "Operation Safe City," arresting 101 individuals in Los Angeles and 107 in Philadelphia.
Other areas targeted include New York City, Denver, Portland, Ore., Baltimore, Cook County, Ill., Santa Clara County, Calif., Washington. D.C., and Massachusetts.
The arrests reflect the Trump administration's desire to crack down on sanctuary cities, which refuse to help federal authorities enforce immigration laws.
President Trump and Attorney General Jeff Sessions have vowed to crack down on localities that do not fully cooperate with the federal government's policy on illegal immigration, arguing that such jurisdictions are more likely to have higher crime rates.
However, the administration has been met with opposition on the issue.
The city of Chicago sued the administration in August over the Justice Department's threat to withhold federal grants from sanctuary cities.
A federal judge blocked the rules requiring sanctuary cities to help enforce federal immigration laws in order to receive funding earlier this month.