N,N-dimethylacetamide (DMAC) which is widely used in chemical industry has been listed as a well-known chemical substance. It could cause reproductive toxicity. Therefore, it is urgent to develop methods for degradation of DMAC to minimize its ecological risk. In this study, copper ferrite (CuFe2O4) magnetic nanoparticles (MNPs) were prepared by sol-gel combustion method for the degradation of DMAC by catalytic ozonation. The results suggest that the synergetic effect between CuFe2O4 MNPs and O-3 in the CuFe2O4/O-3 process was significant and the degradation efficiency of DMAC by CuFe2O4/O-3 process (i.e., 95.4%) was much higher than sole O-3 process (55.4%), sole CuFe2O4 process (0%), CuFe2O4/O-2 process (0%), and Fe2O3/O-3 process (32.1%), which confirmed the superiority of the CuFe2O4/O-3 process. In addition, under the optimal conditions, 95.4% removal of the DMAC (200 mg/L), 30.1% removal of COD, 22.3% removal of TOC could be achieved after 120 min treatment by CuFe2O4/O-3 process. The BOD5/COD (B/C) ratio was also elevated from 0.03 to 0.33, which indicated the significant improvement of biodegradability. Furthermore, the CuFe2O4 MNPs showed high catalytic activity, stability and recyclability for DMAC degradation. In particular, leaching of metal ions from reused CuFe2O4 MNPs was negligible. The radical scavenging experiment certified that the surface hydroxyl groups on CuFe2O4 MNPs are ozone decomposition sites and the dominant oxide species in CuFe2O4/O-3 process is HO. Finally, a possible reaction mechanism of CuFe2O4/O-3 process was proposed according to the present literature and analyses of data. It can be concluded that the high-efficient CuFe2O4/O-3 process was mainly resulted from the combination of sole ozone oxidation, heterogeneous and homogeneous catalytic ozonation. Therefore, the CuFe2O4/O-3 process was a simple, nonhazardous, efficient and promising technology for the degradation of DMAC.