Two intergeneric hybrid snakes (Pituophis catenifer sayi × Pantherophis vulpinus) are described from the midwestern United States; one collected in south central Iowa and the other from southeastern Minnesota. Both specimens are morphologically intermediate between the putative parental species P. c. sayi and P. vulpinus. Hybrid origin was verified by comparing DNA sequence data from the hybrids to the putative parental species. Both hybrid specimens possessed P. c. sayi mitochondrial DNA haplotypes. Examination of the nuclear gene Vimentin (intron 5) showed both specimens were heterozygous at most variable sites confirming their hybrid origin. These snakes represent only the second and third confirmed instances of naturally occurring intergeneric hybridization among squamate reptile species.