The burden of allergic disease is increasing globally, particularly during infancy and early childhood. Now recognised as a major public health concern, Australia has the highest reported prevalence of paediatric food allergy worldwide. Using gold standard oral food challenge outcomes, we have recently shown that 10% of Australian infants are food allergic. Our group has also recently reported that infants with food allergy are twice as likely to develop asthma in later childhood than non-food allergic infants. Despite this high burden, surprisingly little is known about the underlying mechanisms that induce the persistent immune system disruption associated with allergic disease. Using flow- and mass- cytometry analysis of peripheral blood mononuclear cells (PBMCs) collected from a cohort of challenge confirmed food allergic children, this study aimed to phenotype and quantify the functional immune response associated with persistent and transient clinical phenotypes of egg and peanut allergy. We showed that children with persistent egg allergy exhibit a unique innate immune signature, characterised by increased numbers of circulating monocytes and dendritic cells that produce more inflammatory cytokines following endotoxin exposure when compared to infants with transient food allergy. We also revealed, for the first time, that peanut-specific effector and regulatory T cells from peanut allergic infants can be identified based on upregulation of CD154 and CD137, respectively, after in vitro stimulation with peanut allergen. Using mass cytometry, we have also identified the multi-parametric immune signatures that that govern the development of clinical allergy over tolerance in peanut sensitised infants. Our results provide new insights into the underlying biology that drive the development of childhood food allergy that are required for the development of novel intervention and therapeutic strategies.