The spatial boundaries of tissue response to wounding are unknown. Here, we show that in mammals, the ribosomal protein S6 (rpS6) is phosphorylated in response to skin injury, forming a zone of activation surrounding the region of the initial insult. This p-rpS6-zone forms within minutes after wounding and is present until healing is complete. The zone is a robust marker of healing as it encapsulates features of the healing process, including proliferation, growth, cellular senescence, and angiogenesis. A mouse model that is unable to phosphorylate rpS6 shows an initial acceleration of wound closure, but results in impaired healing, identifying p-rpS6 as a modulator but not a driver of healing. Finally, the p-rpS6-zone accurately reports on the status of dermal vasculature and the effectiveness of healing, visually dividing an otherwise homogeneous tissue into regions with distinct properties. Display omitted •Wounding induces phosphorylation of rpS6, leading to formation of the p-rpS6-zone•The zone is induced by DAMPs and layers cell death responses•The zone spatially and temporally delineates the process of healing•Healing processes are limited to the zone, including cellular senescence and angiogenesis Ring and Dworak et al. describe the discovery of an immediate and persistent phosphorylation of rpS6 in response to wounding, forming the p-rpS6-zone. The zone spatially and temporally delineates the processes of healing, appearing within minutes of wounding, encompassing all healing processes (including cellular senescence and angiogenesis) and disappearing upon complete healing.