In this paper, a generalization of Poiseuille’s law for a self-similar fluid flow through a tube having a rough surface is proposed. The originality of this work is to consider, simultaneously, the self-similarity structure of the fluid and the roughness of the tube surface. This study can have a wide range of applications, for example, for fractal fluid dynamics in hydrology. The roughness of the tube surface presents a fractal structure that can be described by the surface fractal noninteger dimensions. Complex fluids that are invariant to changes in scale (self-similar) are modeled as a continuous medium in noninteger dimensional spaces. In this work, the analytical solution of the Navier–Stokes equations for the case of a self-similar fluid flow through a rough “fractal” tube is presented. New expressions of the velocity profiles, the fluid discharge, and the friction factor are determined analytically and plotted numerically. These expressions contain fractal dimensions describing the effects of the fractal aspect of the fluid and of that of the tube surface. This approach reveals some very important results. For the velocity profile to represent a physical solution, the fractal dimension of the fluid ranges between 0.5 and 1. This study also qualitatively demonstrates that self-similar fluids have shear thickening-like behavior. The fractal (self-similarity) nature of the fluid and the roughness of the surface both have a huge impact on the dynamics of the flow. The fractal dimension of the fluid affects the amplitude and the shape of the velocity profile, which loses its parabolic shape for some values of the fluid fractal dimension. By contrast, the roughness of the surface affects only the amplitude of the velocity profile. Nevertheless, both the fluid’s fractal dimension and the surface roughness have a major influence on the behavior of the fluid, and should not be neglected.