The main objective of this study was to examine the determinants of private commercial banks profitability in Ethiopia. To achieve this objective, the researcher used un balanced panel data of ten private commercial banks for ten years obtained from those banks and National Bank of Ethiopia. Financial statements during 2010 - 2019 were used to generate variables. In addition, macro-economic variables gross domestic product and inflation were taken from National Bank of Ethiopia. Equity to asset ratio, loan to asset ratio, non-performing loan, exchange rate, loan to deposit ratio, interest rate, inflation and gross domestic product were used as explanatory variables to profitability. The study used explanatory research design. The researcher included ten private commercial banks which financial statement during the study period. The diagnostic tests of the panel data showed that random effect model was the appropriate model for this study. The result of the random effect model showed that non performing loan, loan to asset ratio and inflation had a statistically significant positive association with the profitability of selected private commercial banks in Ethiopia during the study period. On the other hand, equity to asset ratio and exchange rate statistically significant negative association with the profitability of selected private commercial banks. However, the remaining variables loan to deposit ratio, interest rate and gross domestic product did not show a statistically significant association with profitability of selected private banks. Finally, the researcher recommends that it is better for the management of private commercial banks to give attention and efforts for the variables like; equity to asset ratio, loan to asset ratio, non-performing loan, exchange rate and inflation to improve the profitability of private commercial banks in Ethiopia.