This article describes an efficient electrochemical sensor based on a graphene oxide- manganese dioxide (GO-MnO2) nanocomposite for detecting acetaminophen (AAP) in human fluids. The MnO2- wrapped GO sensing element was prepared by a simple and environmentally friendly co-precipitation method. The prepared GO-MnO2 nanostructure was characterized for its structural, morphological, and functional properties and tested for AAP detection. At a pH of 3, the electrochemical results revealed a high redox process toward AAP due to the transfer of two electrons and protons between the GO-MnO2/ glassy carbon electrode (GO-MnO2/GCE) and AAP. The differential pulse voltammetry (DPV) analytical results showed the precise sensing ability of AAP in a wide linear range [0.125–2000 μM] with superior anti-interference ability. The calculated sensitivity of the GO-MnO2/GCE was 17.04 μAμM−1 cm− 2, and the detection limit (LOD) was 7.042 nM. The sensor exhibited high reliability, good reproducibility, and a good recovery range of 98.47–99.22% in human urine sample analysis.