BACKGROUND: The psychological health of female sex workers (FSWs) has emerged as a major public health concern in many low- and middle-income countries (LMICs). Key risk factors include poverty, low education, violence, alcohol and drug use, human immunodeficiency virus (HIV), and stigma and discrimination. This systematic review and meta-analysis aimed to quantify the prevalence of mental health problems among FSWs in LMICs, and to examine associations with common risk factors. METHOD AND FINDINGS: The review protocol was registered with PROSPERO, number CRD42016049179. We searched 6 electronic databases for peer-reviewed, quantitative studies from inception to 26 April 2020. Study quality was assessed with the Centre for Evidence-Based Management (CEBM) Critical Appraisal Tool. Pooled prevalence estimates were calculated for depression, anxiety, post-traumatic stress disorder (PTSD), and suicidal behaviour. Meta-analyses examined associations between these disorders and violence, alcohol/drug use, condom use, and HIV/sexually transmitted infection (STI). A total of 1,046 studies were identified, and 68 papers reporting on 56 unique studies were eligible for inclusion. These were geographically diverse (26 countries), representing all LMIC regions, and included 24,940 participants. All studies were cross-sectional and used a range of measurement tools; none reported a mental health intervention. Of the 56 studies, 14 scored as strong quality, 34 scored as moderate, and 8 scored as weak. The average age of participants was 28.9 years (age range: 11-64 years), with just under half (46%) having up to primary education or less. The pooled prevalence rates for mental disorders among FSWs in LMICs were as follows: depression 41.8% (95% CI 35.8%-48.0%), anxiety 21.0% (95% CI: 4.8%-58.4%), PTSD 19.7% (95% CI 3.2%-64.6%), psychological distress 40.8% (95% CI 20.7%-64.4%), recent suicide ideation 22.8% (95% CI 13.2%-36.5%), and recent suicide attempt 6.3% (95% CI 3.4%-11.4%). Meta-analyses found significant associations between violence experience and depression, violence experience and recent suicidal behaviour, alcohol use and recent suicidal behaviour, illicit drug use and depression, depression and inconsistent condom use with clients, and depression and HIV infection. Key study limitations include a paucity of longitudinal studies (necessary to assess causality), non-random sampling of participants by many studies, and the use of different measurement tools and cut-off scores to measure mental health problems and other common risk factors. CONCLUSIONS: In this study, we found that mental health problems are highly prevalent among FSWs in LMICs and are strongly associated with common risk factors. Study findings support the concept of overlapping vulnerabilities and highlight the urgent need for interventions designed to improve the mental health and well-being of FSWs.