AbstractPrecise tuning of chemical reactions with predictable and controllable manners, an ultimate goal chemists desire to achieve, is valuable in the scientific community. This tunability is necessary to understand and regulate chemical transformations at both macroscopic and single-molecule levels to meet demands in potential application scenarios. Herein, we realise accurate tuning of a single-molecule Mizoroki-Heck reaction via applying gate voltages as well as complete deciphering of its detailed intrinsic mechanism by employing an in-situ electrical single-molecule detection, which possesses the capability of single-event tracking. The Mizoroki-Heck reaction can be regulated in different dimensions with a constant catalyst molecule, including the molecular orbital gating of Pd(0) catalyst, the on/off switching of the Mizoroki-Heck reaction, the promotion of its turnover frequency, and the regulation of each elementary reaction within the Mizoroki-Heck catalytic cycle. These results extend the tuning scope of chemical reactions from the macroscopic view to the single-molecule approach, inspiring new insights into designing different strategies or devices to unveil reaction mechanisms and discover novel phenomena.