The majority of new and existing cases of hepatitis C virus (HCV) infection occur among people who inject drugs (PWID). Despite safe and efficacious HCV antiviral therapy, uptake remains low in this population. This study examined trends in HCV treatment uptake among a large national sample of PWID attending Australian Needle and Syringe Programs between 1999 and 2011. Annual cross-sectional sero-surveys conducted among PWID since 1995 involve completion of a self-administered questionnaire and provision of a dried blood spot for HCV antibody testing. Multivariate logistic regression identified variables independently associated with HCV treatment uptake among 9478 participants with both self-reported and serologically confirmed prior HCV infection. Between 1999 and 2011, the proportion currently receiving treatment increased from 1.1% to 2.1% (P < 0.001), while the proportion having ever received treatment increased from 3.4% to 8.6% (P < 0.001). Men were significantly more likely than women to have undertaken HCV treatment (P = 0.002). Among men, independent predictors of HCV treatment uptake were homosexual identity and older age; among women, independent predictors included homosexual identity and an incarceration history. Despite increases in HCV treatment among Australian PWID between 1999 and 2011, uptake remains low. Strategies are required to increase the proportion of PWID assessed and treated for HCV infection to address the increasing burden of disease. Specific approaches that target women may also be warranted. Continued surveillance of HCV treatment uptake among PWID will be important to monitor the roll-out of simple, safe and more effective HCV treatments expected to be available in the future.