Abstract Informal settlements regularly experience small and large fires. In South Africa, there were 5940 informal settlement fires during 2017, which is approximately 16 per day. Currently, post-fire investigations are often not being conducted, and close to 40% of all fire causes in informal settlements are labelled as “undetermined”. Conducting post-fire investigations can provide important information to develop better evidence-based responses for improving fire safety in these communities. It is acknowledged that due to the inherent nature of informal settlements high levels of certainty in fire-cause determination are often not possible. After ignition, the onset of flashover occurs rapidly, thus most structures are destroyed within minutes, and often multiple dwellings are involved in a single incident. This paper seeks to apply well-known forensic fire investigation principles (primarily using NFPA 921), to informal settlements to develop a framework and guidelines, in order to (a) identify the fire origin and the fire cause, (b) obtain data on human behaviour in fire, (c) understand the fire spread sequence, and (d) evaluate the effectiveness of suppression and response efforts. The proposed methodology was used to analyse the Imizamo Yethu fire that occurred in 2017. Additionally, the work highlights the challenges associated with conducting such investigations.