We report a photodynamic therapy driven by electrochemiluminescence (ECL). The luminescence generated by Ru(bpy)32+ and co‐reactant tripropylamine (TPA) pair acts as both optical readout for ECL imaging, and light source for the excitation of photosensitizer to produce reactive oxygen species (ROS) in photodynamic therapy (PDT) system. The ECL‐driven PDT (ECL‐PDT) relies on the effective energy transfer from ECL emission to photosensitizer chlorin e6 (Ce6), which sensitizes the surrounding O2 into ROS. The dynamic process of gradual morphological changes, the variation of cell‐matrix adhesions, as well as the increase of cell membrane permeability in the process of ECL‐PDT were monitored under ECL microscopy (ECLM) with good spatiotemporal resolution. Combining real‐time imaging with ECL‐PDT, this new strategy provides not only new insights into dynamic cellular processes, but also promising potential of ECL in clinical applications. A system for photodynamic therapy driven by electrochemiluminescence (ECL) is reported. The ECL generated by the Ru(bpy)32+/TPA pair acts as both the optical readout for the monitoring of the dynamic cellular processes and the light source for the excitation of a photosensitizer to produce cytotoxic ROS.