The effect of surface roughness on the thermohydraulics in minichannels has been studied numerically. Fluid flow (at low Reynolds number) through a typical three-dimensional (3D) channel subjected to constant heat flux (at the bottom) is analyzed incorporating surface roughness on the solid–fluid interfaces characterized by its true random and nonperiodic nature. Two different approaches are adopted to model the rough channel surfaces. Topographic measurements have been performed on a stainless steel minichannel using an optical surface profilometer (OSP) to generate digital replica of the rough surface. Alternatively, the Gaussian function defined by two statistical parameters, namely average roughness and correlation length , are employed to imitate the random nature of rough interface. At the outset, conjugate heat transfer simulations have been performed on the rough channel models and the results are validated against the experimental data. Finally, the effect of surface roughness on both local and global nondimensional performance parameters is analyzed and compared with findings from simulations performed on a similar smooth channel. The outcomes reveal an enhanced friction factor for flow over a rough surface, attributable to the near wall shear rate fluctuations experienced by the flow. Unlike smooth channels, the local Nusselt number exhibits continuous fluctuations along the channel axial length. The fully developed and the average counterparts of the Nusselt number show enhanced magnitudes when compared to the theoretical predictions of the same in a smooth surface channel. This amplification can be attributed to two simultaneously acting factors: augmentation in heat transfer area and chaotic mixing due to flow perturbation. The magnitude of enhancement in terms of fully developed Nusselt number is roughly 1.3 times of its corresponding value in a smooth channel and the factor remains invariant of the supplied heat.