The activity of three [Cp*IrLn] (Cp* = pentamethylcyclopentadienyl) archetypal catalysts ([Cp*Ir (bpy)Cl]Cl (1, bpy = 2,2′-bipyridine), [Cp*Ir(bzpy)(NO3)] (2, bzpy = 2-benzoylpyridine) and [Cp*Ir(H2O)3](NO3)2 (3)) for wateroxidation to molecular oxygen was compared using cerium(IV) ammonium nitrate as a sacrificial oxidant. Kinetic studies were carried out by: i) measuring the depletion of Ce4+ through UV-Vis spectroscopy, ii) directly detecting the evolved oxygen through the Clark electrode and iii) measuring the volume of the evolved oxygen. The kinetics of Ce4+ consumption were zero-order in Ce4+ for catalysts2 and 3, while they were first-order for 1. The order with respect to catalyst was 1 for 1 and 2 while it was 1.5 for 3. As a consequence, 2 (TOFmax = 14.4 min−1) and 3 (TOFmax = 50.4 min−1) were found to be the most active catalysts at low and high catalyst concentration, respectively, while the performance of 1 (TOFmax = 8.6 min−1) increased with increasing the concentration of Ce4+. 1 and 3 were found to be the most robust catalysts at low (3.1 μM, TON = 1240) and high (7.0 μM, TON = 4042) catalyst concentration, respectively. In situ NMR studies were performed under exactly the same conditions of the catalytic experiments. It was observed that Cp* underwent an oxidative degradation, ultimately leading to acetic, formic and glycolic acids. Several Ir-containing intermediates of the degradation process were intercepted and fully characterized in solution through 1D- and 2D-NMR experiments. DFT and NMR studies indicated that the degradation proceeds via an initial double oxidative functionalization of both the quanternary carbon and proton of a Cp* C–CH3 moiety.