Adding a redox-active iridium complex has emerged recently as a new mechanistic pathway to enhance electrochemiluminescence (ECL). But, these redox mediators are costly, require sophisticated synthesis, and induce concomitantly intense ECL emission or a strong background. Herein, we report the use of nortropine N-oxyl (NNO) radical as a non-emissive redox mediator for modulating the co-reactant ECL emission of the archetypical [Ru(bpy)₃]²⁺ luminophore, thanks to its particular reactivity involving hydride transfer from amines. The reversible oxidation of NNO produced its oxoammonium cation and catalyzed the oxidation of tri-n-propylamine (TPrA) and 2-(dibutylamino)ethanol (DBAE) co-reactants. The electrocatalysis of NNO induced a significant decrease in the homogeneous solution-based ECL. However, it offered the versatility to amplify the heterogeneous ECL by 7.3-fold for TPrA or even up to 12.5-fold for DBAE in a bead-based immunosensing format, and by 5.4-fold on single cells. The electrocatalytic mechanism of NNO was further deciphered by the density functional theory (DFT) calculations. The background-free ECL modulation by NNO depends on either the depletion of amine radical or the generation of another alkoxyl radical at the electrode. Such dramatic ECL amplification opens new perspectives for improving the existing ECL bioassays and microscopy and the design of new biosensing schemes.