SummaryAmoeboid cells like leukocytes can enter and migrate within virtually every tissue of the body, even though tissues vary widely in their chemical and mechanical composition. Here, we imaged motile T cells as they colonized peripheral tissues during zebrafish development to ask if cells tailor their migration strategy to their local tissue environment. We found that T cells in most sites migrated with f-actin-rich leading-edge pseudopods, matching how they migratein vitro. T cells notably deviated from this strategy in the epidermis, where they instead migrated using a rearward concentration of f-actin and stable leading-edge blebs. This mode of migration occurs under planar confinementin vitro, and we correspondingly found the stratified keratinocyte layers of the epidermis impose planar-like confinement on leukocytesin vivo. By imaging the same cell type across the body, our data collectively indicates that cells adapt their migration strategy to navigate different tissue geometriesin vivo.