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After graduating from law school, Desai was a law clerk to Chief Judge Mary M. Schroeder of the U.S. Court of Appeals for the Ninth Circuit from 2005 to 2006. From 2006 to 2007, she was an associate at Lewis & Roca in Phoenix, Arizona. In 2007, Desai joined the Phoenix law firm Coppersmith Brockelman as an associate, becoming a partner in 2013. In naming her one of the publication's 2022 "Women of the Year", USA Today called her "a hero of Democratic legal causes," noting her work to launch a recreational marijuana program in Arizona, her lawsuits fighting false claims about the 2020 United States presidential election, and her work to overturn a ban on mask mandates. Desai is a member of the ACLU.
Notable cases
In 2020, Desai represented the Arizona Dispensaries Association in advising it on a marijuana legalization campaign.
On June 15, 2022, President Joe Biden nominated Desai to serve as a United States circuit judge for the Ninth Circuit. Biden nominated Desai to the seat vacated by Judge Andrew D. Hurwitz, who announced his intent to assume senior status upon confirmation of a successor. On July 13, 2022, a hearing on her nomination was held before the Senate Judiciary Committee. On July 28, 2022, her nomination was favorably reported by the committee by a voice vote, with Senators Mike Lee, Ted Cruz, Josh Hawley, and Marsha Blackburn recorded as voting “no”. On August 4, 2022, the United States Senate confirmed her nomination by a 67–29 vote, just 50 days after her initial nomination and the fastest of any court of appeals nomination since the Clinton administration. She received her judicial commission on October 3, 2022. Desai became the first South Asian person to serve on the Ninth Circuit.