The reductive amination of ketones to produce chiral amines is an important transformation in the production of pharmaceutical intermediates. Therefore, industrially applicable enzymatic methods that enable the selective synthesis of chiral amines could be very useful. Using a phenylalanine dehydrogenase scaffold devoid of amine dehydrogenase activity, a robust amine dehydrogenase has been evolved with a single two-site library allowing for the direct production of (R)-1-(4-fluorophenyl)-propyl-2-amine from para-fluorophenylacetone with a kcat value of 6.85 s−1 and a KM value of 7.75 mM for the ketone substrate. This is the first example of a highly active amine dehydrogenase capable of accepting aliphatic and benzylic ketone substrates. The stereoselectivity of the evolved amine dehydrogenase was very high (>99.8% ee) showing that high selectivity of the wild-type phenylalanine dehydrogenase was conserved in the evolution process. When paired with glucose/glucose dehydrogenase, NADH cofactor can be effficiently regenerated and the reaction driven to over 93% conversion. The broad specificity, high selectivity, and near complete conversion render this amine dehydrogenase an attractive target for further evolution toward pharmaceutical compounds and subsequent application.