Numerical simulations are performed to deduce the effects of slip wall and orientation on entropy generation due to natural convection (NC) in a square cavity for Rayleigh number (Ra) = 105. The laterally insulated square cavity, heated at the bottom wall and cooled at the top wall, is subjected to various orientation angles (ϕ) and slip velocities characterized by the Knudsen number (Kn). The two components of entropy generation, i.e., entropy generation due to heat transfer () and entropy generation due to fluid friction (), are separately investigated by varying the orientation from 0 deg to 120 deg in steps of 15 deg and Knudsen number from 0 (no-slip) to 1.5 in steps of 0.5. Evidence indicates that, for most cases considered, entropy generation due to fluid friction () dominates the one due to heat transfer (). It is observed that the slip velocity on the isothermal walls () has a strong influence on whereas the variations in are closely connected to the change in the rate of shear strain. Interestingly, the presence of corner vortices and the secondary circulations near the core of the cavity are also found to affect the variation in entropy generation. The existence of active zones of in the vicinity of isothermal walls and their elongation and migration while changing the orientation is another unique characteristic noticed in this study. A new parameter called maximum velocity ratio (MVR) is also proposed to highlight the variation in velocity components within the enclosure.