In this paper, we present a systematic evaluation about degradation of partially hydrolyzed polyacrylamide (HPAM) in aqueous solution by ionizing radiation to find relationship between HPAM decomposition, viscosity reduction and microstructure of polymer molecules. The viscosity of the two HPAM solution declined rapidly from 5.2 to 3.0 mPa s to 1.4–1.2 mPa s with the adsorbed dose of 0.1 kGy, and then reached the level of pure water at 0.5 kGy. The molecular weight declined remarkably from 1.6 × 107 Da to 1.4 × 105 Da (HPAM1) and from 1.2 × 107 Da to 1.1 × 106 Da (HPAM2) at 0.1 kGy. The HPAM solution changed from pseudoplastic fluid behavior to Newtonian fluid after irradiation. Following ionizing radiation, the presence of anion Na+, Ca2+, Mg2+, anions HCO3- and SO42-(1000–5000 mg/L) and surfactant sodium dodecyl sulfate (SDS) (50–100 mg/L) respectively has slight effect on the rate and extent of viscosity reduction, while CO32- and surfactant petroleum sulfonate exhibit a great negative effect on reducing HPAM viscosity. Ionizing radiation is able to destroy the molecular structure and spatial structure of HPAM. Both the C-C backbones and pendant are attacked. It is proposed that the degradation products include ammonium, aliphatic hydrocarbon, small molecular acids and compounds with double-bond. With the absorbed dose of 0.1 kGy, the micelles-like aggregates are broken into small particles by direct microscope observation, while the stretched and coiled molecular strands shrink and curl to form an irregular network from AFM and SEM observation. The chains break into fragment scattered randomly as increasing dose to 1.0 kGy. Both the diameter size and dispersity of HPAM molecules decreased remarkably after irradiation.·OH is the major active species responsible for HPAM degradation and viscosity reduction. This study contributes to a multiscale understanding the mechanism of ionizing radiation-induced degradation of HPAM in aqueous solution.