Background: Globally, Africa is one of the continents that uses the lowest quantity of agrochemicals in farming. However, unsafe chemical use practices are high among farmers in Africa, posing serious health and environmental consequences. This study seeks to address three questions: (1) What factors motivate/compel smallholder farmers in Ghana to use agrochemicals? (2) What safety precautions or unsafe chemical use practices can be found in the communities? (3) What are the health implications of agrochemical use among smallholder farmers in Ghana? Methodology: The study used purposive and simple random sampling techniques to select 136 individuals for the survey, out of which 31 individuals were eliminated, and 105 participants were selected for in-depth interviews and focus group discussions. Additionally, participants’ observations were collected, workshops were facilitated, and documents analyses were conducted. Qualitative data were analyzed using NVivo software and the quantitative data were analyzed using SPSS version 23.0. Findings: The study found that environmental challenges, activities of NGOs, government policy, lack of or high cost of labor, and competition among farmers were major factors influencing farmers’ decisions to use agrochemicals. Present agrochemical use in Ghana poses a risk to health and the environment. Finally, the study discovered chemical poisoning and low self-reported health quality as major health implications of agrochemical use in the communities.