Adults with comorbidities have faced a high risk from COVID-19 infection. However, Western Australia experienced relatively few infections and deaths from 2020 until early 2022 compared with other OECD countries, as hard border policies allowed for wide-scale vaccination before mass infections began. This research investigated the thoughts, feelings, risk perceptions, and practices of Western Australian adults with comorbidities aged 18–60 years in regard to COVID-19 disease and COVID-19 vaccines. We conducted 14 in-depth qualitative interviews between January and April 2022, just as the disease was starting to circulate. We coded results inductively and deductively, combining the Extended Parallel Process Model (EPPM) and vaccine belief models. Non-hesitant participants believed COVID-19 vaccines were safe and effective at mitigating COVID-19′s threat and subsequently got vaccinated. Vaccine hesitant participants were less convinced the disease was severe or that they were susceptible to it; they also did not consider the vaccines to be sufficiently safe. Yet, for some hesitant participants, the exogenous force of mandates prompted vaccination. This work is important to understand how people’s thoughts and feelings about their comorbidities and risks from COVID-19 influence vaccine uptake and how mandatory policies can affect uptake in this cohort.