Scanning tunneling microscopy (STM) was first designed to image conductive surfaces at the atomic scale resolution and can be used to perform electrical measurements at the single-molecule level [1–5]. Herein, we present a protocol based on single-molecule STM electrical measurements that enables monitoring a chemical reaction at the single molecule level. This was made possible by combining a surface chemistry that enables attaching molecules via self-assembled monolayers on the electrodes with the STM capability to control the distance between electrodes, hence to control the distance and trajectory between the approaching reactants. The reaction studied here is a Diels-Alder reaction between a furan derivative representing the diene (2-methyl-3-furanthiol) which is attached to the tip electrode and a norbornylogous bridge with a terminal double bond as the dienophile attached to the substrate electrode [6,7]. The product molecules are detected by specific current signatures as a consequence of a single product molecule bridging the two STM electrodes. This protocol allows to impose an oriented electrical field of specific magnitude along the approaching reactants at the single-molecule level.