The National Bowel Cancer Screening Program (NBCSP) offers population-based screening for colorectal cancer (CRC) across Australia. The aims of this paper were to highlight the inequities in CRC screening in South Australia (SA) and the system-related barriers and enablers to CRC screening from the perspective of participants identified as having inequitable participation. First, de-identified data for the SA population of the NBCSP were statistically analysed and then mapped. Second, 117 in-depth interviews were conducted with culturally and linguistically diverse (CALD) groups, Indigenous and Anglo-Saxon Australians. Participation rates in the NBCSP were geographically and statistically significantly different (P < 0.0001) on the basis of gender (higher for women), age (higher for older people) and socioeconomic status (higher for more affluent people). The main system-related barriers were the lack of awareness of CRC or CRC screening within these groups, the problems with language due to most of the information being in English and the lack of recommendation by a doctor. This study revealed that inequity exists in the NBCSP participation in SA, and we identified both barriers and facilitators to CRC screening that require action at the level of both policy and practice. There is a large role in primary health care of both recommending CRC screening and facilitating equitable participation.