Terminal thiolate ligands on the synthetic Fe-S-based clusters [Fe4S4(SR)(4)](2-) (R = Et or SPh) or [{MoFe3S4(SPh)(3)}(2)(mu-SPh)(3)](3-) are replaced by chloride in a reaction with PhCOCl to produce [Fe4S4Cl4](2-) and [{MoFe3S4Cl3}(2)(mu-SPh)(3)](3-), respectively. Kinetic studies using stopped-flow spectrophotometry show that, in general, the mechanisms of these reactions in MeCN occur by two pathways. One pathway is independent of the concentration of PhCOCl and involves rate-limiting dissociation of the thiolate ligand. The free thiolate subsequently reacts with PhCOCl to produce PhCOSR and the Cl- which binds to the vacant site on the cluster. The second pathway exhibits a nonlinear dependence on the concentration of PhCOCl and involves initial, rapid binding of PhCOCl to the cluster followed by intramolecular thiolate ligand attack on the coordinated acid chloride. The intermediate in which PhCOCl is bound to the cluster has been detected spectrophotometrically. The ways in which the rates of the reactions between PhCOCl and Fe-S-based clusters are affected by changes of the terminal thiolate, the metal composition of the cluster core, and the protonation state of the cluster have been investigated and are compared with the effect these same changes have on the rates of nucleophilic substitution.