This study presents a formula for estimating the mean flow velocity of the Nile River, Egypt. The proposed formula is presented in the form of the commonly used Manning equation. The derived relationship can be directly incorporated into numerical models and used by hydraulic professionals. The formula is developed using a large database of field measurements from the Nile River and its canals. Its accuracy is assessed using both collected field and laboratory data. The collected field data were used for testing the prediction performance of several equations, and the predictive skill of Karim’s formula is adapted for the Nile River conditions. Despite the complexity of the water flow of the Nile River, which has been significantly altered by humans, and the river’s small energy slopes and very high relative flow depths, the predictions obtained using the proposed formula are consistent with the measurements. The mean normalized errors and root mean square error for the predicted mean velocities of the Nile River are 11.455% and 0.0945 m s−1, respectively.