This study investigated the relationship between drug use and sex work patterns and sex work income earned among street-based female sex workers (FSWs) in Vancouver, Canada. Methods We used data from a sample of 129 FSWs who used drugs in a prospective cohort (2007–2008), for a total of 210 observations. Bivariate and multivariable linear regression using generalized estimating equations was used to model the relationship between explanatory factors and sex work income. Sex work income was log-transformed to account for skewed data. Results The median age of the sample at first visit was 37 years (interquartile range[IQR]: 30–43), with 46.5% identifying as Caucasian, 48.1% as Aboriginal and 5.4% as another visible minority. The median weekly sex work income and amount spent on drugs was $300 (IQR = $100–$560) and $400 (IQR = $150–$780), respectively. In multivariable analysis, for a 10% increase in money spent on drugs, sex work income increased by 1.9% (coeff: 0.20, 95% CIs: 0.04–0.36). FSWs who injected heroin, FSWs with higher numbers of clients and youth compared to older women (<25 versus 25+ years) also had significantly higher sex work income. Conclusions This study highlights the important role that drug use plays in contributing to increased dependency on sex work for income among street-based FSWs in an urban Canadian setting, including a positive dose-response relationship between money spent on drugs and sex work income. These findings indicate a crucial need to scale up access and availability of evidence-based harm reduction and treatment approaches, including policy reforms, improved social support and economic choice for vulnerable women.