Abstract Background: The cancer registry of Bulawayo (Zimbabwe) operated for 15 years in the preindependence period (1963–77), and was restarted in 2011. This allows comparison of incidence of cancers over a period of almost 50 years. Methods: Age-standardized rates, with SEs, were calculated for 1963–1972 and 2011–2015. Detailed results are presented for those cancers for which there was a significant (P < 0.05) change in the rates between the two periods. Results: There were declines in the rates of those cancers previously known to be common in East and Southern Africa (esophagus, liver, bladder), and the emergence of cancers associated with “westernization” of lifestyles (breast, prostate, large bowel). Cancers related to infection with HIV–AIDS (Kaposi sarcoma, non-Hodgkin lymphoma, eye cancers) have come to comprise a much larger proportion of the total burden, and cancer of the cervix (also AIDS-related) has shown a large increase in incidence—as elsewhere in sub-Saharan Africa (SSA). More surprising is the decline in cancer of the lung—formerly very high, but by 2011–2015, despite little change in the prevalence of smoking, rates were low—close to the average for SSA. This may relate, in part, to a decline in the numbers of miners, and ex-miners, residing in the city. Conclusions: The changes in incidence are largely explained by differences in past exposure to environmental risk factors. Impact: Few datasets from SSA can document temporal changes in the cancer epidemic on the continent. There are some anticipated observations, as well as unexpected findings meriting further investigation.