Burkholderia pseudomallei is a Gram-negative soil saprophyte with the potential to cause melioidosis, an opportunistic disease with a high mortality potential. Periodic case reports of melioidosis in or imported from Africa occur in the literature dating back decades. Furthermore, statistical models suggest Western sub-Saharan Africa as a high-risk zone for the presence of B. pseudomallei. A recent case report from the United Kingdom of a returning traveler from Ghana highlights the need for environmental studies in Ghana. We examined 100 soil samples from a rice farm in south-central Ghana. Soil was subjected to selective enrichment culture for B. pseudomallei using threonine-basal salt solution with colistin (TBSS-C50) and erythritol medium, as described in the literature. Bacterial cultures were identified with standard biochemical tests, a rapid antigen detection assay, and real-time PCR specific for B. pseudomallei. Of the 100 soil samples, 55% yielded cultures consistent with B. pseudomallei on Ashdown's agar as well as by capsular polysaccharide antigen production. This is the first confirmatory report of culture-confirmed B. pseudomallei in the environment of Ghana. Our study emphasizes the need for further exploration of the burden of human melioidosis in Ghana. We recommend that local clinicians familiarize themselves with the diagnosis and clinical management of melioidosis, while laboratories develop capacity for the safe isolation and identification of B. pseudomallei. IMPORTANCE We present the first confirmation of the presence of B. pseudomallei in the environment of Ghana. This study will bring attention to a disease with the potential to cause significant morbidity and mortality in Ghana, but which has gone completely unrecognized until this point. Furthermore, this work would encourage local clinicians to familiarize themselves with the diagnosis and clinical management of melioidosis and laboratories to develop capacity for the safe isolation and identification of B. pseudomallei.