The study examined the relationship between macroeconomic variables and deposit money banks (DMBs) credit creation in Nigeria over the period 1981-2020. The data used in this study was secured from the Central Bank of Nigeria statistical bulletins of various issues. Specifically, we pay attention on how exchange rate (EXR), unemployment rate (UEMR), inflation rate (INF), GDP growth rate (GDPGR), and interest rate (INT) affects DMBs loans and advances (LnDMBLA). We employed the descriptive statistics, stationarity test, ARDL framework, and the Granger Causality at the 95% confidence limit. For the stationarity test, the variables were integrated at different orders giving rise to the ARDL F-bound test that shows evidence of co-integrating relationship. The ARDL long run form test shows that EXR, GDPGR, and INT are positive but insignificant while UEMR and INF are negative but significant to LNDMBLA. Also, the ARDL ECM shows that errors in the short-run are corrected at a speed of 12.16% in the long run. For Granger Causality, there is only a directional movement from UEMR to LnDMBLA but none for EXR, INF, GDPGR, and INT. We conclude that inflation and unemployment rates significantly affect DMBs loan and advances. We recommended that the CBN ensure timely and equitable distribution of foreign currency to businesses in order to mitigate naira-US dollar fluctuations. In addition, the CBN, through appeals and incentives, advises DMBs to extend more credit to SMEs in order to reduce the number of unemployed people