Climate change is adversely affecting smallholder farming households in Africa and in particular in Ghana because their activity depends on climate-regulated water resources. This study examined the vulnerability of smallholder maize farming households to climate change in the Brong-Ahafo region of Ghana by employing the Livelihood Vulnerability Index with particular emphasis on access to and utilization of water resources. The primary data were based on 150 maize farming households, complemented by secondary data on rainfall and temperature over the period 1983–2013. To assess the climate change effects and related vulnerability, a comparative analysis was performed for the Wenchi and Techiman municipalities in the Brong-Ahafo region. The empirical results revealed that farming households in Wenchi municipality were more vulnerable to climate change and weather variability in terms of food, water, and health than those in Techiman municipality. Furthermore, farming households in Wenchi municipality were more vulnerable in terms of adaptive capacity, taking into account the socio-demographic aspects, social networks, and livelihoods of households in the municipality than those in Techiman municipality. These results have implications for the initiation and implementation of climate change adaptation and household resilience projects by the government, donor agencies, and other related organizations in the two municipalities in the region.