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In this article, we investigate the fractional Volterra-Fredholm integro-differential equations. These equations appear in several applications such as control theory, biology, and particle dynamics in physics. We derive a numerical method based on the operational matrix method to solve this class of integro-differential equations. We prove the existence and uniqueness of the exact solution. Additionally, we demonstrate the uniform convergence of the numerical solutions to the exact solution. We present several numerical examples to show the numerical efficiency of the proposed method. In the first example, we choose a linear problem and find that the approximate solution converges to the exact solution when the number of block pulse functions is very large. In the next two examples, we consider the nonlinear case and compute the L2-local truncation error since exact solutions are not available. The error was of order 10−12. Furthermore, we sketch the graph of the approximate solutions for different values of the fractional derivative to observe the influence of the fractional derivative on the profile of the solutions. Theoretical and numerical results show that the proposed method is accurate and can be applied to other nonlinear problems in science. [ABSTRACT FROM AUTHOR]