Climate change and variability is one of the great challenges facing farming households in Ghana. The main objective of this study is to assess the vulnerability of smallholder maize farming households to climate variability in the Eastern region. Specifically, the study investigates the vulnerability of households to climate variability, the determinants of households’ livelihood vulnerability level, the adoption level of adaptation strategies to climate variability and the determinants of the choice of those strategies and finally households’ constraints to climate variability adaptation strategies in the Yilo Krobo Municipality and Ayensuano District in the Eastern Region of Ghana. Primary data was collected using structured questionnaires and focus group discussions whereas the Secondary data for climate were collected from the Meteorological Agency, Ghana. Fifteen (15) respondents each were sampled randomly from 10 communities making 150 respondents. The Livelihood Vulnerability Index (LVI) is used to analyze households’ vulnerability to climate variability while Generalized Least Square is used to estimate the determinants of household vulnerability level. Multinomial Logistic regression model is employed for the determinants of the choice of adaptation strategies. The main software used is Stata (13). The results of the LVI score for Yilo Krobo is 0.363 and that of Ayensuano is 0.390 while the LVI-IPCC is 0.028 for Yilo Krobo and 0.031 for Ayensuano, all the two approaches indicating that households in Ayensuano are most vulnerable to the impacts of climate variability. Both Ayensuano and Yilo Krobo are most vulnerable in the natural disaster and climate variability component (0.528 for Ayensuano and 0.459 for Yilo Krobo) but least vulnerable in food component of the LVI (0.227 for Ayensuano and 0.202 for Yilo Krobo). The results of the GLS regression show gender, farm size, access to credit and temperature perception to be the factors that statistically influence household vulnerability in Yilo Krobo while farming experience, formal extension and hired labour are found to significantly influence vulnerability of households in Ayensuano district. The pooled sample show farming experience, access to credit, formal extension, temperature perception and hired labour to be the determinants of households’ vulnerability level. The most adopted climate adaptation option in the area is found to be improved varieties and breeds strategies (38%) follow by recommended agricultural practice strategies (36%) with soil related strategies been the least adopted adaptation strategies (27%).