Climate change poses significant challenges to vulnerable communities worldwide, with Malawi being particularly susceptible to extreme weather events such as floods, droughts, and erratic rainfall patterns. This study focuses on Mzuzu City, the third-largest urban center in Malawi, emphasizing its ecological significance and the imperative for robust climate resilience strategies. Central to this resilience are Indigenous and Local Knowledge Systems (ILKS), which encompass traditional practices, cultural beliefs, and ecological wisdom developed over generations. Utilizing political ecology as the theoretical framework, this research employs a qualitative methodology to explore the integration of ILKS into Mzuzu’s climate resilience frameworks, highlighting the interplay between socio-political dynamics and environmental practices. Through semi-structured interviews, focus group discussions, and participant observations with community leaders, farmers, and women, the study identifies key adaptive strategies such as traditional rainwater harvesting, crop diversification, agroforestry, community-based irrigation systems, integrated pest management, preservation of indigenous seed varieties, and strengthening social cohesion. These strategies demonstrate how ILKS contribute to sustainable resource management, enhanced agricultural productivity, and social resilience against climatic adversities. However, the integration of ILKS with modern practices faces challenges, including limited formal education access, policy marginalization, and external technological encroachments. The findings underscore the necessity of inclusive policymaking and community empowerment to leverage ILKS effectively. By bridging traditional knowledge with contemporary climate science, this study advocates for a more holistic and culturally resonant approach to climate resilience in Mzuzu City. The research contributes to broader discussions on sustainable development and offers a model for integrating ILKS in climate adaptation strategies across similar contexts in Malawi.