This study examined the pesticide use behavior of farmers along the White Volta Basin in the Upper East Region of Ghana, using the Theory of Planned Behavior (TPB) to explore the underlying factors. A multistage sampling procedure was used to select 300 food crop farmers, from whom data was collected and analyzed using the frequency, percentage, means, standard deviation and partial least squares structural equation modeling (PLS-SEM) techniques. The results revealed that attitude, subjective norm, and perceived behavioral control compositely accounted for approximately 29% of the variation in farmers’ intention towards the safe use of pesticides, whereas intention and perceived behavioral control explained 38% of the variation in farmers’ behavior towards safe pesticide use. Additionally, attitude and perceived behavioral control were found to significantly impact the intention and behavior of farmers towards safe pesticide use in the study area. Accordingly, it is recommended that stakeholders, including agricultural extension agents (AEAs), agricultural input retailers, the Environmental Protection Agency (EPA), and the Plant Protection and Regulatory Services Directorate (PPRSD), collaborate to develop training curricula aimed at improving the behavior of the farmers in the study area. The training regimes should incorporate extension training methods, for example, method and result demonstrations, which are known to improve the attitudes and behaviors of farmers.