Climate change has become a global phenomenon in recent times. The geographical characteristics of Northern Ghana exposes the region to the adverse consequences of climate variability. The northern sector of Ghana is characterized by a unimodal rainfall pattern occurring between May and September. Agricultural productivity and food security are threatened by the effects of climate change. Climate change adaptation strategies are expected to reduce the negative impacts of climate change through improvements in the resilience of the existing agricultural systems. The study sought to investigate the factors influencing smallholder farmers’ choice of adaptation strategies to reduce the negative impact of climate variability in the Gushegu Municipality of the Northern Region of Ghana. Since farmers in the study district adopt a mix of adaptation strategies to reduce the negative impact of climate change, the choice of a set of bundle of adaptation strategies becomes a multivariate decision. This study therefore adopted the multivariate probit econometric technique to establish the relationships between climate change adaptation strategies (dependent variables) and the factors influencing the choice of the adaptation strategies (independent variables). With a sample size of 175 farm households, the study revealed that the dominant climate change adaptation strategies in order of popularity were; mixed farming, use of improved varieties of crops and animal breeds, income diversification, adjusting planting time, crop rotation, and use of farm belts. The independent variables were; age, gender, size of household, farm experiences, level of education, membership of farmer-based organization, access to credit, and income level of the farmers. The study recommends that farmers should be supported in terms of financial and technical assistance to improve their adaptive capacity to deal with the adverse effects of climate change. Sensitization campaigns against climate change are essential to equip farmers with the requisite know-how to minimize agricultural losses associated with climate change.