This study majorly considered establishing the relationship that existed among the Nigerian-Naira (NGN) Exchange Rate and External Reserve, Inflation Rate, GDP Growth, Public Debt, Unemployment Rate and Exports for the period, (1981-2021). Also, the macroeconomic variables that influenced the NGN exchange rate fluctuations were determined. Multiple linear regression and correlation analyses were employed in this study. Results showed that the significant variables that influenced the NGN exchange rate fluctuations were External Reserve, Public Debt and Unemployment Rate; and each of them had very strong significant positive relationships with NGN exchange rate fluctuations. It was equally revealed that about 97% of the total variations in the NGN exchange rate fluctuations, from 1981 to 2021, were accounted for by variations in External Reserve, Public Debt and Unemployment Rate; while about 3% of the total variations in the NGN exchange rate could be attributed to other macroeconomic factors outside the ones used in this study. It was concluded that External Reserve, Public Debt and Unemployment Rate were the most macroeconomic factors that influenced the Nigerian-Naira exchange rate fluctuations from 1981 to 2021.