AbstractRegeneration of functional surfaces after damage or contamination could extend the life time of devices. Such regeneration can be achieved by layer shedding (like a lizard shedding its skin). In this work, triggered self‐regeneration of functional surfaces by an external stimulus is presented. Polymer multilayer stacks are assembled alternatingly from discrete 20–300 nm thick functional layers and depolymerizable interlayers, which are used as sacrificial layers. The sacrificial layers are depolymerizable poly(benzyl carbamates) end‐capped with 4‐hydroxy‐2‐butanone. Their depolymerization is triggered by alkaline pH, at which the end‐cap is cleaved. This initiates a 1,6‐elimination cascade of the polymer backbone, during which CO2 is released. Thus, the layer shedding is driven synergistically by mass transport and buoyancy forces. Proof‐of‐concept is achieved using poly(styrene) as a model functional layer, and also studied for hydrophilic, antimicrobially active poly(oxanorbornene) layers. The multilayer assembly and disassembly process is monitored by ellipsometry, Fourier transform infrared spectroscopy (FTIR), optical microscopy, and atomic force microscopy. FTIR spectra taken after degradation are confirmed the regeneration of the surface functionality.