The current study discusses the irreversibility analysis for the Couette flow of non-Newtonian fluids between two asymmetrically heated parallel plates for two different flow configurations viz., under the application of a weak pressure gradient and for a relatively strong pressure gradient. The plates are kept at different constant temperatures, while the effect of viscous dissipation is included in the analysis. The study explores the combined consequences of the rheological effect of the fluids, the movement of the upper plate, and the magnitude of the externally applied pressure gradient on the irreversibility generation rate of the system as manifested by the variation of the volumetric entropy generation number, irreversibility distribution ratio, and the Bejan number. Intricate interplay between the effects of fluid friction and heat transfer in dictating the irreversibility of the system is highlighted for different degrees of asymmetrical wall heating and upper-plate velocity. The study further shows that, for a given degree of asymmetrical wall heating, the irreversibility generation rate alters with the alteration in the rheological behaviour of the fluid.