Due to the severe restrictions imposed by legislative frameworks, the removal of polyacrylamide (PAM) rapidly and effectively from produced wastewater in offshore oilfields before discharge is becoming an urgent challenge. In this study, a novel advanced oxidation process based on plasma operated in the gas–liquid interface was used to rapidly decompose PAM, and multiple methods including viscometry, flow field-flow fractionation multi-angle light scattering, UV–visible spectroscopy, and attenuated total reflectance-Fourier transform infrared spectroscopy were used to characterize the changes of PAM. Under a discharge voltage of 25 kV and pH 7.0, the PAM concentration decreased from 100 to 0 mg/L within 20 min and the total organic carbon (TOC) decreased from 49.57 to 1.23 mg/L within 240 min, following zero-order reaction kinetics. Even in the presence of background TOC as high as 152.2 mg/L, complete removal of PAM (100 mg/L) was also achieved within 30 min. The biodegradability of PAM improved following plasma treatment for 120 min. Active species (such as O3 and H2O2) were produced in the plasma. Hydroxyl radical was demonstrated to play an important role in the degradation of PAM due to the inhibitory effect observed after the addition of an ·OH scavenger, Na2CO3. Meanwhile, the release of ammonia and nitrate nitrogen confirmed the cleavage of the acylamino group. The results of this study demonstrated that plasma, with its high efficiency and chemical-free features, is a promising technology for the rapid removal of PAM.