Silver nanoparticles (AgNPs) modified boron and sulfur co-doped reduced graphene oxide (B, S@rGO) were prepared by one-pot hydrothermal method for the first time. The combination between AgNPs and B, S@rGO decreases stacking of B, S@rGO and decreases the particle size of AgNPs; in addition, it enhances the effective surface area and electro-catalytic activities of the nanocomposite. The morphology and structure of AgNPs/B, S@rGO were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron microscope (XPS), Raman spectroscopy, UV-Vis spectroscopy, thermogravimetric analysis (TGA), and Brunauer–Emmett–Teller (BET). The electro-catalytic activity of AgNPs/B, S@rGO was studied using cyclic voltammetry (CV), electron impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). Because of the synergetic effects of AgNPs and B, S@rGO, the modified electrode displayed considerably enhanced sensitivity to ivermectin (IVM) determination. The voltammetric response is linear over the range of 0.3–60.0 nM with LOD (S/N = 3) of 0.1 nM. The proposed sensor exhibited good selectivity, reproducibility, and long-term stability. The modified electrode was used to analyze IVM in injections, urine, and tap-water with recoveries % of 99.6–105.8% and RSDs of 2.14–3.65%.