Rates of sexually transmitted infections (STIs) in the United States have continued to increase for nearly a decade as state and local health departments across the country have divested from sexual health services. The resulting closure of municipal STI clinics has led many uninsured and underinsured patients to rely on emergency departments for their sexual health needs. The authors describe the creation of the novel Sexual Wellness Clinic at University of Chicago Medicine in February 2019. The clinic provides comprehensive sexual health care to establish linkage to pre-exposure prophylaxis (PrEP) for HIV, primary care, and other essential services to patients presenting to the emergency department for STI care. Since operationalization, the Sexual Wellness Clinic has served 560 unique patients; 50.5% (n = 283) were cisgender male and 49.5% (n = 277) were cisgender female. The majority of patients were African American (93.4%, n = 523), non-Hispanic or Latinx (96.1%, n = 538), between 18 and 29 years old (62.3%, n = 350), and had Medicaid or were uninsured (84.3%, n = 472). New syphilis diagnoses were identified in 23.5% (132/560) of patients; gonococcal and chlamydial infections were confirmed in 14.6% (82/560) and 13.4% (75/560) of patients, respectively. Same-day PrEP was initiated for 16.1% (90/560) of patients, of which 56.7% were cisgender female. The Sexual Wellness Clinic identified unique candidates for PrEP, notably a large proportion of Black cisgender women; however, further work is needed to support the ongoing PrEP cascade. Identifying these new populations with untreated STIs and other HIV risk factors for targeted, innovative interventions is integral to HIV elimination and STI control efforts.