In this study, we demonstrate the influence of crystallinity and morphology on the analytical performance of various Cu2MoS4 (CMS) nanocatalysts‐based electrochemical sensors for the high‐efficiency detection of Ofloxacin (OFX) antibiotic. The electrochemical kinetics parameters including peak current response (ΔIp), peak‐to‐peak separation (ΔEp), electrochemically active surface area (ECSA), electron‐transfer resistance (Rct), were obtained through the electrochemical analyses, which indicate the single‐crystalline nature of CMS nanomaterials (NMs) is beneficial for enhanced electron‐transfer kinetics. The morphological features and the electrochemical results for OFX detection substantiate that by tuning the tube‐like to plate‐like structures of the CMS NMs, it might noticeably enhance multiple adsorption sites and more intrinsic active catalytic sites due to the diffusion of analytes into the interstitial spaces between CMS nanoplates. As results, highly single‐crystalline and plate‐shaped morphology structures of CMS NMs would significantly enhance the electrocatalytic OFX oxidation in terms of onset potential (Eonset), Tafel slope, catalytic rate constant (kcat), and adsorption capacity (Γ). The CMS NMs‐based electrochemical sensing platform showed excellent analytical performance toward the OFX detection with two ultra‐wide linear detection concentration ranges from 0.25 – 100 and 100 – 1000 μM, a low detection limit of 0.058 μM, and an excellent electrochemical sensitivity (0.743 µA µM–1 cm–2).