The fabrication of materials that are responsive to endogenous gasotransmitter molecules (i.e., nitric oxide, hydrogen sulfide, and carbon monoxide) has emerged as an area of increasing research interest. In the case of nitric oxide (NO), o-phenylenediamine derivatives have traditionally been employed due to their ability to react with NO in the presence of oxygen (O2) with the formation of benzotriazole residues. Herein, we report the synthesis of a novel NO-responsive polymer containing aromatic primary amine groups derived from p-phenylenediamine groups (i.e., isomers of o-phenylenediamine). A new NO-responsive monomer, N-(4-aminophenyl)methacrylamide (p-NAPMA), was first synthesized via the amidation of one of the primary amine groups in the p-phenylenediamine with methacrylic anhydride. Notably, the p-NAPMA monomer can efficiently react with NO in aqueous solution in the presence of O2 with the generation of phenyldiazonium groups rather than benzotriazole moieties. While the resultant phenyldiazonium residues were relatively stable in aqueous solution, they were highly sensitive to UV irradiation (i.e., λmax = 365 nm) which gave the formation of phenol derivatives. After incorporation into a thermoresponsive block copolymer using reversible addition-fragmentation chain transfer (RAFT) polymerization, the resulting diblock copolymer, poly(ethylene glycol)-b-(N-isopropylacrylamide-co-p-NAPMA) (PEG-b-P(NIPAM-co-p-NAPMA)), was rendered with unique NO- and UV-responsive characteristics. Specifically, the NO-triggered transformation of p-NAPMA moieties into phenyldiazonium residues dramatically elevated the lower critical solution temperature (LCST) of the block copolymer due to increased water solubility of phenyldiazonium residues at neutral pH (i.e., pH 7.4). Further, subsequent UV irradiation significantly decreased the LCST due to the formation of relatively hydrophobic phenol derivatives from the hydrophilic phenyldiazonium intermediate. These results demonstrate, for the first time, that NO-responsive polymers can be synthesized without the necessity of incorporating o-phenylenediamine groups and that a further solubility switch can be stimulated by irradiation with ultraviolet light.