The current multicountry outbreak of mpox in 2022 is the first occurrence of widespread transmission in nonendemic countries. Prior cases in the United States involved exposure through foreign travel or direct contact with infected rodents. Reports of the current outbreak have predominately described spread through sexual encounters between cis-gender men who have sex with men. We report a unique case of mpox in which the transmission occurred through oral sex between 2 transgender men, with a short incubation period and progressive asynchronous emergence of lesions. Continued analysis of transmission routes and awareness will improve timely prevention, diagnosis and treatment.