In this study, the impact of energy, agriculture, macroeconomic and human-induced indicators on environmental pollution from 1971 to 2011 is investigated using the statistically inspired modification of partial least squares (SIMPLS) regression model. There was evidence of a linear relationship between energy, agriculture, macroeconomic and humaninduced indicators and carbon dioxide emissions. Evidence from the SIMPLS regression shows that a 1% increase in crop production index will reduce carbon dioxide emissions by 0.71%. Economic growth increased by 1% will reduce carbon dioxide emissions by 0.46%, which means that an increase in Ghana's economic growth may lead to a reduction in environmental pollution. The increase in electricity production from hydroelectric sources by 1% will reduce carbon dioxide emissions by 0.30%; thus, increasing renewable energy sources in Ghana's energy portfolio will help mitigate carbon dioxide emissions. Increasing enteric emissions by 1% will increase carbon dioxide emissions by 4.22%, and a 1% increase in the nitrogen content of manure management will increase carbon dioxide emissions by 6.69%. The SIMPLS regression forecasting exhibited a 5% MAPE from the prediction of carbon dioxide emissions.