The Treasury on Wednesday blacklisted Miguel Angel de Anda Ledezma, 40, and Ricardo Gonzalez Sauceda, 27.
De Anda is accused of overseeing the procurement of guns and ammunition for the gang.
Gonzalez, an alleged second-in-command of CDN, is currently in Mexican custody. He was arrested in February.
"In working toward the total elimination of cartels to Make America Safe Again, the Trump administration will hold these terrorists accountable for their criminal activities and abhorrent acts of violence," Treasury Secretary Scott Bessent said in a statement.
Formerly known as Los Zetas, CDN is a notorious criminal organization based in the Mexican states of Tamaulipas, Coahuila and Nuevo Leon. It has been connected to human, drug and arms trafficking as well as money laundering and vehicle and oil theft.
In February, the State Department designated CDN and seven other cartels as foreign terrorist organizations and specifically designated global terrorists at the direction of President Donald Trump, who, on his first day in office, signed an executive order targeting the criminal organizations.
Trump campaigned on securing the border from both criminal cartels and irregular migration.
"The United States remains committed to protecting our nation by keeping illicit drugs off our streets and degrading the ability of cartels to arm themselves, a critical step toward the total elimination of these organizations," State Department spokesperson Tammy Bruce said in a statement.
"Today's action further demonstrates the Trump administration's unwavering commitment to protecting our local communities and the safety of the American people."
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