Summary What is already known about this topic?Before 2018, no ceftriaxone-resistant Salmonella Typhi cases had been identified in the United States. Extensively drug-resistant Salmonella Typhi, susceptible only to azithromycin and carbapenems, has caused a typhoid fever outbreak in Pakistan since 2016. What is added by this report?During February 2018–August 2019, 33 cases of ceftriaxone-resistant Salmonella Typhi were detected in the United States. Whole genome sequencing of isolates identified two distinct clusters, associated with travel to Pakistan (30 cases) and Iraq (three). What are the implications for public health practice?Vaccination and food and water precautions can help prevent typhoid fever. Clinicians and public health officials should remain vigilant for ceftriaxone-resistant Typhi in patients who have traveled to Pakistan, Iraq, or neighboring countries.