The ULK1 complex, consisting of the ULK1 protein kinase itself, FIP200, Atg13, and Atg101, controls the initiation of autophagy in animals. We determined the structure of the complex of the human Atg13 HORMA (Hop1, Rev7, Mad2) domain in complex with the full-length HORMA domain-only protein Atg101. The two HORMA domains assemble with an architecture conserved in the Mad2 conformational heterodimer and the S. pombe Atg13-Atg101 HORMA complex. The WF finger motif that is essential for function in human Atg101 is sequestered in a hydrophobic pocket, suggesting that the exposure of this motif is regulated. Benzamidine molecules from the crystallization solution mark two hydrophobic pockets that are conserved in, and unique to, animals, and are suggestive of sites that could interact with other proteins. These features suggest that the activity of the animal Atg13-Atg101 subcomplex is regulated and that it is an interaction hub for multiple partners. Display omitted •Structure of human Atg13-Atg101 HORMA dimer refined at 1.6 Å resolution•Atg13 safety belt anchored, ordered, and consistent with stable heterodimer•WF finger is in a closed and inactive conformation•Hydrophobic pockets marked by benzamidines suggest function as interaction hub The human ULK1-FIP200-Atg13-Atg101 complex initiates autophagy and is a promising target for aging, neurodegeneration, cancer, and infection. Qi et al. describe a structure of the HORMA dimer of human Atg13 and Atg101 that shows how they assemble and might coordinate binding of substrates and regulatory proteins.