Prisons and other closed facilities create opportunities for transmission of human immunodeficiency virus (HIV) and viral hepatitis during detention and after release. We conducted a systematic review and meta-analysis of peer-reviewed publications (2005-2015) to describe the prevalence of HIV, hepatitis C virus, and hepatitis B virus among key populations in prisons worldwide and to compare estimates of infection with those of other prison populations. Most data were reported for people who inject drugs (PWID; n = 72) and for men who have sex with men (MSM; n = 21); few data were reported on sex workers (SW; n = 6), or transgender women (n = 2). Publications were identified from 29 countries, predominantly middle- and high-income countries. Globally, PWID had 6 times the prevalence of HIV (pooled prevalence ratio (PPR) = 6.0, 95% CI: 3.8, 9.4), 8 times the prevalence of hepatitis C virus (PPR = 8.1, 95% CI: 6.4, 10.4), and 2 times the prevalence of hepatitis B virus (PPR = 2.0, 95% CI: 1.5, 2.7) compared with noninjecting prisoner populations. Among these articles, only those from Iran, Scotland, Spain, and Italy included the availability of methadone therapy; 2 articles included information on access to needle exchange programs by PWID detainees. HIV prevalence was more than 2 times higher among SW (PPR = 2.6, 95% CI: 2.2, 3.1) and 5 times higher among MSM (PPR = 5.3, 95% CI: 3.5, 7.9) compared with other prisoners. None of these articles reported HIV prevention coverage among SW or transgender women; 1 described HIV and sexually transmitted infection screening for MSM in prison. Prevention programs specific to key populations are important, particularly for populations that are criminalized and/or may cycle in and out of prison.