The acceleration characteristics of fragments generated from explosively-driven cylindrical shells are important issues in warhead design. However, there is as yet no reasonable theory for predicting the acceleration process of a specific metallic shell; existing approaches either ignore the effects of shell disintegration and the subsequent gas leakage on fragment acceleration or treat them in a simplified manner. In this paper, a theoretical model was established to study the acceleration of discrete fragments under the combined effect of shell disintegration and gas leakage. Firstly, an equation of motion was developed, where the acceleration of a cylindrical shell and the internal detonation gas was determined by the motive force impacting the inner surface of the metallic cylinder. To account for the force decrease induced by both the change in fragment area after the shell disintegrates and the subsequent drop in gas pressure due to gas leakage, the equation of motion was then associated with an equation for the locally isentropic expansion of the detonation gas and a modified gas-leakage equation. Finally, theoretical analysis was conducted by solving the associated differential equations. The proposed model showed good agreement with experimental data and numerical simulations, indicating that it was suitable for predicting the acceleration of discrete fragments generated from a disintegrated warhead shell. In addition, this study facilitated a better understanding of the complicated interaction between fragment acceleration and gas outflow.