A sensitive, rapid and simple flow-injection chemiluminescence (CL) system based on the light emitted from KMnO4–cadmium sulfide quantum dots (CdS QDs) reaction in the presence of cetyltrimethylammonium bromide (CTAB) in acidic medium was developed as a CL probe for the sensitive determination of atenolol. Optical and structural features of CdS QDs capped with l-cysteine, which synthesized via hydrothermal approach, were investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), photoluminescence (PL), and UV–Vis spectroscopy. The CL intensity of KMnO4–CdS QDs–CTAB was remarkably enhanced in the presence of trace level of atenolol. Under optimum experimental conditions, there is a linear relationship between the increase in CL intensity of KMnO4–CdS QDs–CTAB system and atenolol concentration in a range of 0.001 to 4.0 mg L− 1 and 4.0 to 18.0 mg L− 1, with a detection limit (3σ) of 0.0010 mg L− 1. A possible mechanism for KMnO4–CdS QDs–CTAB-atenolol CL reaction is proposed. To prove the practical application of the KMnO4–CdS QDs–CTAB CL method, the method was applied for the determination of atenolol in spiked environmental water samples and commercial pharmaceutical formulation. Furthermore, corona discharge ionization ion mobility spectrometry (CD-IMS) technique was utilized for determination of atenolol.