A key element in understanding how human milk proteins support the health and development of the neonate is to understand how individual proteins are affected during digestion. In the present study, a dynamic gastric model was used to simulate infant gastric digestion of human milk, and a subsequent proteomic approach was applied to study the behavior of individual proteins. A total of 413 human milk proteins were quantified in this study. This approach demonstrated a high degree of variability in the susceptibility of human milk proteins to gastric digestion. Specifically this study reports that lipoproteins are among the class of slowly digested proteins during gastric processes. The levels of integral lysozyme C and partial lactadherin in milk whey increase over digestion. Mucins, ribonuclease 4, and macrophage mannose receptor 1 are also resistant to gastric digestion. The retention or enhancement in whey protein abundance can be ascribed to the digestive release of milk-fat-globule-membrane or immune-cell enclosed proteins that are not initially accessible in milk. Immunoglobulins are more resistant to digestion compared to total milk proteins, and within the immunoglobulin class IgA and IgM are more resistant to digestion compared to IgG. The gastric digestion of milk proteins becomes more apparent from this study.