We found that cyclometalated cyclopentadienyl iridium(III) complexes are uniquely efficient catalysts in homogeneous hydrogenation of oximes to hydroxylamine products. A stable iridium C,N-chelation is crucial, with alkoxy-substituted aryl ketimine ligands providing the best catalytic performance. Several Ir-complexes were mapped by X-ray crystal analysis in order to collect steric parameters that might guide a rational design of even more active catalysts. A broad range of oximes and oxime ethers were activated with stoichiometric amounts of methanesulfonic acid and reduced at room temperature, remarkably without cleavage of the fragile N-O bond. The exquisite functional group compatibility of our hydrogenation system was further demonstrated by additive tests. Experimental mechanistic investigations support an ionic hydrogenation platform, and suggest a role for the Bronsted acid beyond a proton source. Our studies provide deep understanding of this novel acidic hydrogenation and may facilitate its improvement and application to other challenging substrates.