Female sex workers (FSW) have a high prevalence of substance use and HIV, but the impact of substance use on HIV treatment engagement is not well established. We evaluated the association between alcohol and marijuana use and sub-optimal HIV treatment engagement outcomes among HIV-infected FSW in Lilongwe, Malawi. We enroled FSW using venue-based recruitment into a cross-sectional evaluation assessing substance use and HIV treatment engagement. Seropositive FSW, identified through HIV rapid testing, received rapid CD4 count and viral load testing. We used Poisson regression with robust variance estimates to ascertain associations of alcohol and marijuana use with sub-optimal HIV treatment outcomes: (1) lack of ART use among previously diagnosed, ART-eligible FSW and (2) viral nonsuppression among FSW on ART. Of previously diagnosed, ART-eligible FSW (n = 96), 29% were not using ART. Patterns of hazardous drinking were identified in 30%, harmful drinking in 10%, and alcohol dependence in 12%. ART-eligible FSW with harmful drinking or alcohol dependency were 1.9 (95% CI: 1.0, 3.8) times as likely to not use ART compared to FSW without harmful or dependent drinking. Among those on ART, 14% were virally nonsuppressed. The prevalence ratio for viral nonsuppression was 2.0 (95% CI: 0.6, 6.5) for harmful drinkers and alcohol-dependent FSW. Over 30% of ART-eligible FSW reported using marijuana. Marijuana-using FSW were 1.9 (95% CI: 0.8, 4.6) times as likely to not use ART compared to FSW who were not using marijuana. Given the high prevalence of alcohol use and its association with lack of ART use, ART uptake and alcohol reduction strategies should be tailored for alcohol-using FSW in Malawi.