Hydrogels are of interest for a wide range of applications from sensors to drug delivery and tissue engineering. Self-immolative polymers, which depolymerize from end-to-end following a single backbone or end-cap cleavage, offer advantages such as amplification of the stimulus-mediated cleavage event through a cascade degradation process. It is also possible to change the active stimulus by changing only a single end-cap or linker unit. However, there are very few examples of self-immolative polymer hydrogels, and the reported examples exhibited relatively poor stability in their nontriggered state or slow degradation after triggering. Described here is the preparation of hydrogels composed of self-immolative poly(ethyl glyoxylate) (PEtG) and poly(ethylene glycol) (PEG). Hydrogels formed from 2 kg/mol 4-arm PEG and 1.2 kg/mol PEtG with a light-responsive linker end-cap had high gel content (90%), an equilibrium water content of 89%, and a compressive modulus of 26 kPa. The hydrogel degradation could be turned on and off repeatedly through alternating cycles of irradiation and dark storage. Similar cycles could also be used to control the release of the anti-inflammatory drug celecoxib. These results demonstrate the potential for self-immolative hydrogels to afford a high degree of control over responses to stimuli in the context of smart materials for a variety of applications.