Dextran methacrylate (Dex-MA) is a biodegradable polysaccharide derivative that can be cross-linked by ionizing radiation. It is therefore considered a potential replacement for synthetic hydrophilic polymers in current radiation technologies used for synthesizing hydrophilic cross-linked polymer structures such as hydrogels, mainly for medical applications. This work is focused on the initial steps of radiation-induced cross-linking polymerization of Dex-MA in water. Rate constants of two major transient water radiolysis products—hydroxyl radicals (•OH) and hydrated electrons (eaq−)—with various samples of Dex-MA (based on 6–500 kDa dextrans of molar degree of substitution or DS with methacrylate groups up to 0.66) as well as non-substituted dextran were determined by pulse radiolysis with spectrophotometric detection. It has been demonstrated that these rate constants depend on both the molecular weight and DS; reasons for these effects are discussed and reaction mechanisms are proposed. Selected spectral data of the transient species formed by•OH- andeaq−-induced reactions are used to support the discussion. The kinetic data obtained in this work and their interpretation are expected to be useful for controlled synthesis of polysaccharide-based hydrogels and nanogels of predefined structure and properties.