A sensitive, low cost and novel electrochemical sensor based on 1‐ethyl‐3‐methylimidazolium 1,1,2,2‐tetrafluoroethanesulfonate ionic liquid (EmimTFES) combined with multi‐walled carbon nanotubes (MWCNTs) and zinc oxide nanoparticles (ZnONPs) in order to modify the glassy carbon electrode (GCE), has been developed for the first time. It was assessed that this sensor can be used for the rapid detection of the pharmaceutically antiretroviral drug zidovudine (ZDV). The characterization of ZnONPs, MWCNTs‐ZnONPs and MWCNTs‐ZnONPs‐EmimTFES was performed using Transmission electron microscopy (TEM), Ultraviolet Visible spectrophotometer (UV‐Vis), Fourier‐transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD), and Thermogravimetric analysis (TGA). The electrochemical of behaviour of MWCNTs‐ZnONPs‐EmimTFES‐GCE was studied using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods. The proposed sensor shows high electrocatalytic activity towards ZDV reduction over the concentration range of 0.2 μM to 2.0 μM. In addition, the limit of detection (LOD) of 0.0029 μM and limit of quantification (LOQ) of 0.0416 μM was obtained. Under optimal conditions the ionic liquid‐based sensor showed high selectivity, stability and sensitivity for ZDV detection, making it a suitable sensor for rapid determination of ZDV.