Duffy joined the Criminal Division of the U.S. Department of Justice as a trial attorney in 1993, working first for the Money Laundering Section and then for the Narcotics and Dangerous Drug Section. In 1997, she moved to the U.S. Attorney’s Office for the Southern District of California, with the rank of Assistant United States Attorney. There, she served in the Narcotics Enforcement Section until being promoted in 2007 to the position of Deputy Chief of the General Crimes Section.[3] She is best known for her prosecution of members of the Arellano-Felix drug cartel.[4]
On February 24, 2010, Duffy was nominated by President Barack Obama to serve as U.S. Attorney for the Southern District, which covers San Diego and Imperial counties. The Senate Judiciary Committee approved her nomination unanimously on May 27, 2010;[5] she gained unanimous approval from the full Senate the following day.[4]
In October 2011, she joined with the three other U.S. Attorneys from California to announce a controversial crackdown on medical marijuana dispensaries, which are permitted under California state law but not under federal law.[6]