In developing countries, informal settlements are mainly located in floodplains and wetlands, hence, they are frequently affected by floods. The objective of this study is to demonstrate a methodological approach that integrates the community members’ local and indigenous knowledge and GIS-based Multi-Criteria Decision Making using the Analytic Network Process (ANP) in mapping flood vulnerability in an informal settlement. The study was conducted in Quarry Road West informal settlement located in Durban, South Africa. A mixed-method approach that involved a household survey (n = 359), interviews with key informants (n = 10) and focus group discussions (n = 2) were used in this study. The results of this study showed that there is a spatial differentiation of flood vulnerability in the study area. Households along the Palmiet River were highly vulnerable to flooding. A section of the settlement called Mcondo 1 was also highly vulnerable to flooding while maMsuthu had low flood vulnerability. The sensitivity analysis results showed that changing the indicator weights, correspondingly, affected the output of the flood vulnerability map. Therefore, this study can serve as a guide for decision-makers on how to elicit adequate community participation and comprehensively integrate local and indigenous knowledge with Geographical Information System in mapping flood vulnerability in informal settlements.