Data on antifungal utilization trends are important for encouraging antifungal stewardship. This study explored the use of antifungal agents for systemic application and the impact of reimbursement policy changes in Australia. We analyzed national data from the Australian Pharmaceutical Benefits Scheme (PBS) (2005–2016) and determined patterns of use over time and the impact of reimbursement decisions using an interrupted time-series model. From 2005–2016, there was an increase in the use of most antifungals, especially fluconazole, itraconazole, and posaconazole. Ketoconazole was the most commonly dispensed systemic antifungal agent (46.0%) prior to being removed from the PBS list and being replaced by fluconazole (69.8%). The PBS event “Fluconazole and itraconazole restrictions eased” led to the immediate increased use of fluconazole (0.025/1,000 per day), with both the highest rates and numerical increases attributed to obstetricians and gynecologists (1,969%; 1,851 dispensed prescriptions), as well as dermatologists (1,723%; 1,689 dispensed prescriptions) in 2010 and 2016. This is the first Australian national longitudinal estimate of systemic antifungal use. Our findings show an overall increase in the prescription of most antifungals during the investigated period, with reimbursement decisions impacting utilization. These data provide a baseline to inform the development of national antifungal guidelines and policies to encourage more targeted antifungal stewardship.