Land use, land cover, and climate change impacts are current global challenges that are affecting many sectors, like agricultural production, socio-economic development, water quality, and causing land fragmentation. In developing countries like Uganda, rural areas with high populations dependent on agriculture are the most affected. The development of sustainable management measures requires proper identification of drivers and impacts on the environment and livelihoods of the affected communities. This study applied drivers, pressure, state, impact, and response model in the L. Kyoga basin to determine the drivers and impacts of land use, land cover, and climate change on livelihoods and the environment. The objective of this study was to determine the drivers and impacts of land use, land cover, and climate changes on the environment and livelihoods in the L. Kyoga basin and suggest sustainable mitigation measures. Focus group discussions, key informant interviews, field observations, and literature reviews were used to collect data. Population increase and climate change were the leading drivers, while agriculture and urbanization were the primary pressures, leading to degraded land, wetlands, and forests; loss of soil fertility, hunger, poverty, poor water quality, which are getting worse. The local communities, government, and non-government institutions had responses to impacts, including agrochemicals, restoration, and conservation approaches. Although most responses were at a small/pilot scale level, most responses had promising results. The application of policies and regulations to manage impacts was also found to be weak. Land use, land cover changes, and climate change occur in the L. Kyoga basin with major impacts on land, water, and community livelihoods. With the observed increase in climate change and population growth, drivers and impacts are potentially getting worse. Therefore, it is essential to expand interventions, provide relief, review policies and regulations, and enforce them. The findings are helpful for decisions and policy-makers to design appropriate management options.