This study aims to provide an assessment of Iran’s CO2 emission using a macroeconomic-climate assessment. It uses two complementary quantitative approaches, namely energy-economy-environment indicators and econometric analyses. Based on the latest available data (1971–2015), evidence shows that change in Iran’s total primary energy supply can significantly explain the variability of CO2 emission in Iran, while energy intensity and CO2 intensity cannot significantly explain its variability. Increases in energy intensity are mostly related to substantial increases in energy consumption rather than increases in economic activity. Econometric results show that variability of CO2 emissions is best explained by population and per capita GDP than any other tested variable.