Study design: Cross-sectional population-based survey for the Australian cohort of the International Spinal Cord Injury (InSCI) Community Survey. Objectives: To differentiate subgroups of people with spinal cord injury (SCI) who self-report good and poor overall quality of life (QoL) using domains of the International Classification of Functioning (ICF), and to evaluate how these factors contribute to QoL when considered together, while controlling confounders. Setting: Australian survey data from four state-wide SCI services, one government insurance agency, and three not-for-profit consumer organisations. Methods: Explanatory factors for QoL were compared between participants reporting poor vs. good QoL. Path models estimated total, direct and mediated contributions from each explanatory factor to QoL ratings after accounting for confounders. Results: Most participants (62%) reported good or very good QoL, 12% reported poor or very poor QoL. When explanatory factors were considered together, the strongest total effects on QoL involved social integration (+0.36 SDs), subjective social position (+0.29), secondary health condition burden (−0.28), activity/participation problem burden (−0.26), day-to-day assistance (−0.26), mental health (+0.18), pain (−0.16), self-efficacy (+0.15), vitality (+0.14) and environmental barriers (−0.11). Effects of social integration, mental health, vitality, self-efficacy, pain and activity/participation problems were partly or wholly direct. Conclusion: Opportunities to improve QoL in people with SCI exist at every level of the health system. Virtually all aspects of the ICF framework make a substantive difference to QoL outcomes. Social and psychological factors and ability to complete desired activities have key direct effects and influence effects of secondary health condition burden and environmental barriers.