The classical Helmholtz–Smoluchowski (HS) model of electroosmosis holds for homogeneously charged interfaces in contact with a fluid layer bearing an equal and opposite net charge. However, inhomogeneities in the surface charge and topography are inevitable, either as practical materials and fabrication artefacts, or at times as deliberately introduced modulations for flow control. In an effort to arrive at an analytically tractable theoretical framework for addressing the underlying electro-mechanical coupling, here, we generalize the traditional HS theory to an extent where both the surface charge and topographies may bear arbitrary and independent periodic forms. Using a spectral-asymptotic approach, we further arrive at closed-form expressions for describing the resulting electroosmotic pumping for topographic features with small characteristic amplitude to pattern period ratio, as relevant for most practical scenarios. We subsequently execute full-scale numerical simulations without any restrictions on the surface charge and topography variations to assess the efficacy of the theoretical framework. The corresponding test beds include distinctive signature patterns – for example, a square-wave surface charge distribution on trapezoidal pit topographies. Our results reveal that the charge–topography interplay induces an anisotropic flow drift, deviating from the classical HS paradigm. This, in turn, provides new quantitative insights into highly selective electroosmotic flow control via judicious design of the charge and topographical patterns, resulting in controllable accentuation, attenuation, nullification, deflection and even complete reversal of the flow. Our analysis further establishes a provision of estimating the zeta potentials of naturally ‘contaminated’ surfaces, as well as explaining the electrophoresis of large inhomogeneous particles; a paradigm that remained to be explored thus far.