A fully predictive one-dimensional mechanistic model was developed for describing the hydrodynamics of power-law fluids in trickle-bed reactors. The model is a generalization of the slit approach to the case of non-Newtonian fluids obeying Ostwald de Waele rheological behavior. Without recourse to adjustable parameters, the proposed model enabled prediction of the experimental values of (i) total two-phase total pressure drop and total liquid holdup in the trickle flow regime, (ii) frictional pressure drop in single-phase flows through packed beds, and (iii) total liquid holdup in gravity driven liquid downflow and stagnant gas through packed beds. Parametric simulations guided by knowledge of the behavior of highly viscous Newtonian liquids in trickle beds highlighted the capability of the model in the simulation and design of trickle flow operation using power-law fluids.