Increasing human activities in coastal areas of Ghana have led to the degradation of many surface waterbodies, with significant consequences for the ecosystems in the affected areas. Thus, this degradation extremely affects the health of ecosystems and disrupts the essential services they provide. The present study explored the use of benthic macroinvertebrates as an indicator of estuarine degradation along the coast of Ghana. Water and sediment samples were collected bimonthly from Ankobra, Kakum and Volta estuaries for physicochemical parameters, nutrients and benthic macroinvertebrates. The findings revealed the dominance of pollution-tolerant taxa such as Capitella sp., Nereis sp., Heteromastus sp., Tubifex sp., Cossura sp. and Chironomous sp. in Kakum Estuary while pollution-sensitive taxa such as Scoloplos sp., Euridice sp., Lumbriconereis sp. and Pachymelania sp. in the Volta Estuary. The species-environment interactions showed dissolved oxygen, temperature, salinity, orthophosphate, nitrates, ammonium, electrical conductivity, turbidity, and chemical oxygen demand as the most significant parameters that complement the use of benthic macroinvertebrates as indicators of environmental quality in the studied estuaries. There were correlations of some benthic macroinvertebrate taxa with environmental factors in the estuaries suggesting low, moderate and high levels of pollution in the Volta, Kakum and Ankobra estuaries, respectively. Nevertheless, the study finds Kakum Estuary to be the ecologically healthiest estuary than the Volta and Ankobra Estuaries. Therefore, the study has shown benthic macroinvertebrates as a key indicator of ecosystem health alterations, and it is recommended that they should be incorporated with other environmental data for pollution monitoring in Ghanaian coastal waters.