Applications based on near-infrared femtosecond laser-induced plasma in biological materials involve numerous ionization events that inevitably mediate physicochemical effects. Here, the physical chemistry underlying the action of such plasma is characterized in a system of biological interest. We have implemented wavefront shaping techniques to control the generation of laser-induced low electron density plasma channels in DNA aqueous solutions, which minimize the unwanted thermo-mechanical effects associated with plasma of higher density. The number of DNA base modifications per unit of absolute energy deposited by such cold plasma is compared to those induced by either ultraviolet or standard ionizing radiation (γ-rays). Analyses of various photoinduced, oxidative, and reductive DNA base products show that the effects of laser-induced cold plasma are mainly mediated by reactive radical species produced upon the ionization of water, rather than by the direct interaction of the strong laser field with DNA. In the plasma environment, reactions among densely produced primary radicals result in a dramatic decrease in the yields of DNA damages relative to sparse ionizing radiation. This intense radical production also drives the local depletion of oxygen.