Ovotransferrin (OVT) is the main protein component of egg white responsible for initial gelation due to its high thermal susceptibility. Co-aggregation of lysozyme (LYZ) is involved in OVT aggregate formation at low temperatures during pasteurization. Undesirable formation of aggregates limits the degree of thermal processing that can be applied to egg white products. However, the characteristics of co-aggregates of OVT and LYZ have not been elucidated. Here, we determined the thermal co-aggregation process of OVT and LYZ in terms of protein composition, structure, intermolecular forces, and morphology. The amount of LYZ involved in co-aggregates was dependent on the amount of aggregated OVT regardless of the mixing ratio. Native LYZ had the capability of precipitating soluble OVT aggregates by non-covalent association. The co-aggregates of OVT and LYZ formed colloidal particles with a large network, which was not observed in systems consisting of either protein alone. The hierarchical co-aggregation of OVT and LYZ started from the aggregation of OVT involving LYZ non-covalently, which suppresses electrostatic repulsion between soluble OVT aggregates, followed by the growth of insoluble aggregates by disulfide bond crosslinkage between the soluble aggregates. These results provide information regarding efficient pasteurization and thermal processing of hen egg white. Display omitted •Co-aggregation of OVT and LYZ was derived from the aggregation of OVT itself.•The aggregation rate of OVT increased in the presence of LYZ.•The amount of LYZ in co-aggregates was proportional to that of aggregated OVT.•Native LYZ precipitated soluble aggregates of OVT by non-covalent association.•The network structure of aggregates depended on the ratio of aggregated proteins.