Abstract Rapid globalization has created an increasing demand for miniaturized electronic devices that can detect biologically important molecules, biomarkers and toxins present in the environment to ameliorate living standards. This has been achieved primarily by integrating nanomaterials with electrochemical sensor technology. Among the different classes of nanomaterials, covalent organic frameworks (COFs), a crystalline porous polymer comprising a predetermined shape, have gained considerable attention due to their large surface area, tuneable porosity and extended π-conjugation, which makes them suitable electrocatalysts in designing electrochemical sensors. This review brings to light the various multifaceted insights on COFs-based electrochemical sensors for the detection of biologically significant molecules and environmental toxicants. Then, the recent advances in the fabrication of COF-based electrochemical sensor matrices are comprehensively summarized along with their performance. The merits associated with COFs which include their intrinsic electrocatalytic activity, synthetic versatility, and ease of functionalization towards construction of electrochemical sensors and the sensing mechanism is systematically introduced. Finally, the current challenges in COFs-based electrochemical sensors are discussed along with the potential avenues for future research. This includes the demand for multiplexed biosensors with enhanced analytical performance and shelf-life, and ease of integration with microfluidic devices, and wearable & wireless database technologies for remote-sensing applications.