The European rabbit, Oryctolagus cuniculus, is threatened within its native range, yet it is a highly successful colonizing pest species across its worldwide introduced range, causing large economic losses and widespread environmental degradation. To date, there has been no long-term empirical evidence documenting the relative roles of climatic, epidemiological and biological factors in limiting life-history determinants of rabbit range and abundance. Using 12 years of capture–mark–recapture data from their exotic range in Australia, we constructed candidate Cormack–Jolly–Seber models to test the influence of environmental, competition and disease conditions on rabbit survival and recruitment. Our results show that: (i) population-level disease infection rate has the largest overall impact on rabbit survival, explaining 80% of variance in survival rates; (ii) environmental as well as epidemiological conditions constrain rabbit survival, especially for younger animals; (iii) temporal variation in rabbit kitten recruitment patterns are best described by a combination of climate, competition and disease settings (accounting for 68% of variance), while temperature alone has a strong negative influence on kitten recruitment; and (iv) recruitment responds positively to rabbit haemorrhagic disease, but negatively to myxomatosis – the former, probably being mediated through a disease driven effect on intraspecific competition for food. A strengthened understanding of climate change impacts on rabbit range and abundance can be achieved by accounting explicitly for potential synergisms between disease dynamics and climate. In this analysis, we provide the first step towards such an attempt for this important mammal species. Integrated approaches of this kind are essential for future forecasts of rabbit range and abundance, offsetting the conservation threat faced by O. cuniculus in its native range, and achieving effective management in exotic habitats.