This study investigated herpes simplex virus type 2 (HSV-2) seroprevalence utility as a predictor of HIV epidemic potential among female sex workers (FSWs) globally. We updated and analyzed a systematically-assembled database for paired HSV-2 and HIV seroprevalence measures among FSWs. The study identified 231 paired HSV-2/HIV prevalence measures from 40 countries. The pooled mean HIV prevalence using meta-analysis increased from 3.7% (95% CI 0.3-9.9%) among populations of FSWs with HSV-2 prevalence < 25% to 18.7% (95% CI 14.1-23.8%) among those with HSV-2 prevalence 75-100%. HIV prevalence was negligible in FSWs with HSV-2 prevalence ≤ 20% suggesting a threshold effect. Multivariable meta-regressions explained > 65% of HIV prevalence variation, and identified a strong positive HSV-2/HIV association. Compared to populations of FSWs with HSV-2 prevalence < 25%, adjusted odds ratios (AORs) of HIV infection increased from 2.8 (95% CI 1.2-6.3) in those with HSV-2 prevalence 25-49%, to 13.4 (95% CI 6.1-29.9) in those with HSV-2 prevalence 75-100%. HSV-2 is a strong predictor of HIV epidemic potential among FSWs. HSV-2 prevalence of 25-49% indicates potential for intermediate-intensity HIV epidemics, with higher levels indicative of large epidemics. HSV-2 surveillance could inform HIV preparedness in countries where HIV prevalence among FSWs is still limited or at zero-level.