Targeted covalent inhibitors (TCIs) are irreversible enzyme inhibitors that are designed to first bind to a targeted enzyme’s active site reversibly using non-covalent interactions between the molecular scaffold of the inhibitor and the surrounding amino acid residues of the enzyme’s binding site. They then form a covalent bond between the inhibitor’s electrophilic warhead and a nucleophilic amino acid residue located inside of the binding pocket. Cysteine (Cys), a redox-sensitive thiol, is found in many enzyme active sites and is used as the target for many current TCIs in clinical application. Electrophilic warheads such as acrylamides and chloroacetamides are known to readily undergo thiol-addition, and although they are commonly used in the development of enzyme inhibitors, few previous studies have explored the mechanism of thiol-addition and the intrinsic reactivities of these moieties. In this work, a robust kinetic assay was developed to perform mechanistic studies of thiol-addition to the electrophilic warhead derivatives N-phenylacrylamide (NPA), N-acryloylpiperidine (AcrPip), and N-phenylchloroacetamide (NPC). By reacting these warhead derivatives with thiol nucleophiles having various pKa values, we were able to construct Brønsted-type plots, resulting in shallow positive βNucRS- values for NPA, AcrPip and NPC (βNucRS- = 0.07 ± 0.04, 0.11 ± 0.03, and 0.21 ± 0.07, respectively), meaning that these electrophiles are relatively insensitive to thiolate nucleophilicity. However, while the trend in their reactivity across thiolate nucleophilicity is similar, their intrinsic reactivity was found to be vastly different. In conjunction with the Brønsted-type plot, temperature, ionic strength, and kinetic isotope effects were studied to afford information about the rate-limiting transition state and elucidate the mechanism of thiol-addition. NPA and AcrPip were found to undergo very similar thiol-additions, consistent with the microscopic reverse of the E1cbrev elimination, whereas NPC follows an SN2 type addition, consistent with the intuitive mechanism of addition to a haloacetamide.