The development of disposable electrode-based sensors is of great importance for the electrochemical monitoring of toxic pollutants in wastewater systems, which are often present and mutually inhibiting during sample detection. In this work, a distinctive approach was taken to use an electrochemical heterostructure sensor with chemically reduced nickel boride (Ni3B) nanoparticles anchored in two-dimensional (2D) layered cobalt selenide (CoSe) nanosheets. The prepared hybrid structure (2D CoSe/Ni3B) enables large active sites and a strong synergistic effect between nanostructures to improve the electrocatalytic activity in the detection of water pollutant 5-nitroquinoline (5-NQ) with a disposable screen-printed carbon electrode (SPCE). The 2D CoSe/Ni3B/SPCE exhibits a reduction peak potential of −0.63 V for 5-NQ, with an increased reduction peak current compared to that of other electrodes. The fabricated disposable strip electrode is suitable for the electrochemical testing of pollutants. The proposed hybrid 2D CoSe/Ni3B/SPCE disposable sensor showed a wide linear range of 0.2–378 μM and a low detection limit of 0.042 μM for 5-NQ. The developed 2D CoSe/Ni3B hybrid nanostructure-based disposable sensor efficiently detects 5-NQ in hazardous water contaminants by voltammetric analysis and showed acceptable recoveries. Based on the results, it is believed that the proposed work provides a clear idea for the fabrication of transition metal-based metal boride and selenide heterostructures with excellent catalytic activity for the electrochemical detection of various pollutants in real-time monitoring.