α-Methoxyimino-β-keto esters are reported to undergo highly enantioselective catalytic transfer hydrogenation using the Noyori-Ikariya complex RuCl(p-cymene)[(S,S)-Ts-DPEN] in a mixture of formic acid-triethylamine and dimethylformamide at 25 °C. The experimental study performed on over 25 substrates combined with computational analysis revealed that a Z-configured methoxyimino group positioned alpha to a ketone carbonyl leads to higher reactivity and mostly excellent enantioselectivity within this substrate class. Density functional theory calculations of competing transition states were used in rationalizing the origins of enantioselectivity and the possible role of the methoxyimino group in the reaction outcome.