Phagocytosis is initiated by lateral clustering of receptors, which in turn activates Src-family kinases (SFKs). Activation of SFKs requires depletion of tyrosine phosphatases from the area of particle engagement. We investigated how the major phosphatase CD45 is excluded from contact sites, using single-molecule tracking. The mobility of CD45 increased markedly upon engagement of Fcγ receptors. While individual CD45 molecules moved randomly, they were displaced from the advancing phagocytic cup by an expanding diffusional barrier. By micropatterning IgG, the ligand of Fcγ receptors, we found that the barrier extended well beyond the perimeter of the receptor-ligand engagement zone. Second messengers generated by Fcγ receptors activated integrins, which formed an actin-tethered diffusion barrier that excluded CD45. The expanding integrin wave facilitates the zippering of Fcγ receptors onto the target and integrates the information from sparse receptor-ligand complexes, coordinating the progression and ultimate closure of the phagocytic cup. Display omitted •Tyrosine phosphatases are excluded from sites of phagocytosis•An expanding diffusion barrier prevents phosphatase access to sites of phagocytosis•Integrins activated by phagocytic receptors generate the diffusion barrier•Activated integrins bridge sparse phagocytic receptors and coordinate phagocytosis To create the large zone of Src-family kinase (SFK) phosphorylation required for phagocytosis, a cascade of integrin activation, emanating from antigen contact sites, generates an expanding actin-based diffusion barrier that restricts the access of the bulky phosphatase molecules that target SFK.