Abstract Background Residents of informal settlements in Sub-Sahara Africa (SSA) are vulnerable to the health impacts of climate change. Little is known about the knowledge, attitudes and practices (KAP) of inhabitants of informal settlements in SSA regarding climate change and its health impacts. The aim of this study was to investigate how inhabitants of an informal settlement in SSA experience climate change and its health impacts and assess related knowledge, attitudes and practices. The study was conducted in Mukuru informal settlement in Nairobi City County, Kenya. Methods A cross-sectional study was conducted in September 2021 using a structured, semi-closed KAP questionnaire. Inclusion criteria were ≥ 18 years of age and living in one of the three main sections in Mukuru: Kwa Njenga, Kwa Reuben or Viwandani. By spinning a pen at the geographic centre of each section, a random direction was selected. Then, in every second household one individual was interviewed, creating a representative mix of ages and genders of the local community. To assess participant characteristics associated with climate change knowledge multivariable logistic regression was used. Thematic content analysis was performed for qualitative responses. Results Out of 402 study participants, 76.4% (n = 307) had heard of climate change before the interview, 90.8% (n = 365) reported that climate change was affecting their community, and 92.6% (n = 372) were concerned with the health-related impact of climate change. Having lived in Mukuru for more than 10 years and living in a dwelling close to the riverside were factors significantly associated with having heard of climate change before (aOR 3.1, 95%CI 1.7 – 5.8 and aOR 2.6, 95%CI 1.1 – 6.1, respectively) and experiencing a climate change related impact on the community (aOR 10.7, 95%CI 4.0 – 28.4 and aOR 7.7; 95%CI 1.7 – 34.0, respectively). Chronic respiratory conditions, vector-borne diseases, including infectious diarrhoea, malnutrition and cardiovascular diseases were identified by respondents as climate related health risks. Conclusions Most respondents were knowledgeable about climate change and were experiencing its (health-related) impact on their community. This study provides insights which may prove useful for policy makers, intervention planners and researchers to work on locally adapted mitigation and adaption strategies.