We show that despite very similar crystallographic properties and work function values in bulk Fe and Cr, epitaxial films of these metals on Nb:SrTiO 3 (001) exhibit completely different heterojunction electronic properties. The Cr/SrTiO 3 interface is ohmic, whereas Fe/SrTiO 3 forms a Schottky barrier with a barrier height of 0.50 eV. This difference arises because of variations in interface chemistry. In contrast to Cr [Chambers, S. A. et al., Adv. Mater. 2013, 25, 4001.], in-diffused Fe exhibits a +2 oxidation state and occupies Ti sites in the perovskite lattice, resulting in negligible charge transfer to Ti, upward band bending, and Schottky barrier formation. The differences between Cr and Fe are understood by performing first-principles calculations of the energetics of defect formation, which corroborate experimental results.