In the present study, the facile and synergistic approach for electrochemical sensing of paracetamol (PA) drug was demonstrated by hydrothermally synthesized copper oxide-copper ferrite nanohybrid composite supported on reduced graphene oxide (CuO-CuFe2O4@rGO) glassy carbon electrode. The surface texture and structural information of the electrode material were examined by FE-SEM, HR-TEM, and X-ray diffraction techniques, whereas the electrochemical sensing application of paracetamol oxidation was investigated by amperometric method. The average crystallite size of CuO-CuFe2O4 was calculated from XRD data and found to be 35.45 nm. The fabricated sensor exhibited a higher sensitivity of 970.26 μA.mM−1.cm−2 along with a lower limit of detection (LOD) and limit of quantification (LOQ) of 7.0 μM and 25 μM, respectively, with a linear dynamic range of 10–1200 μM. Furthermore, the CuO-CuFe2O4@rGO modified sensor showed excellent anti-interferents ability, long-term stability and reproducibility towards electro-oxidation of paracetamol drug. Moreover, it can be efficiently applied for the analysis of paracetamol in biological samples. Finally, the synthesized nanocomposite material was validated to be a competent electrocatalyst for electrochemical sensing application of paracetamol.