Registration of pesticides for use in Ghana is based on prospective environmental risk assessment (ERA) to assess the risks of future pesticide use on the environment. The present study evaluated whether pesticides currently used by Ghanaian farmers may harm the aquatic and terrestrial environment under day-to-day farm practice by performing a 1st tier ERA for terrestrial and aquatic environment and a 2nd tier ERA for the aquatic environment using existing scenarios and models. Results of the 1st tier risk assessment indicated that in the investigated regions in south Ghana, many pesticides might pose an acute risk to aquatic ecosystems adjacent to the treated fields while lambda cyhalothrin, chlorpyrifos, cypermethrin, dimethoate, mancozeb, carbendazim, sulphur, maneb and copper hydroxide may pose the highest chronic risks. Butachlor, dimethoate and carbendazim may pose acute risks to the terrestrial soil ecosystem, while glyphosate, chlorpyrifos, imidacloprid, dimethoate, mancozeb, carbendazim, maneb, copper hydroxide and cuprous oxide may pose the highest chronic risks. Many insecticides and some fungicides may pose acute risks to bees and terrestrial non-target arthropods. The 2nd tier acute aquatic risk assessment showed that most risks were substantiated using species sensitivity distribution (SSD). Actual pesticide use was a factor of 1.3–13 times higher than the recommended label instructions, indicating a general practice of overdosing. The case study shows that the PRIMET model in combination with the SSD concept may offer pesticide registration authorities in Ghana a means to assess environmental risks associated with pesticide usage in a user-friendly and cost-effective manner.