The role of the corrinoid cofactor in reductive dehalogenation catalysis by tetrachloroethene reductive dehalogenase (PceA) of Sulfurospirillum multivorans was investigated using isotope analysis of carbon and chlorine. Crude extracts containing PceA—harboring either a native norpseudo-B₁₂ or the alternative nor-B₁₂ cofactor—were applied for dehalogenation of tetrachloroethene (PCE) or trichloroethene (TCE), and compared to abiotic dehalogenation with the respective purified corrinoids (norpseudovitamin B₁₂ and norvitamin B₁₂), as well as several commercially available cobalamins and cobinamide. Dehalogenation of TCE resulted in a similar extent of C and Cl isotope fractionation, and in similar dual-element isotope slopes (ε_C/ε_Cl) of 5.0–5.3 for PceA enzyme and 3.7–4.5 for the corrinoids. Both observations support an identical reaction mechanism. For PCE, in contrast, observed C and Cl isotope fractionation was smaller in enzymatic dehalogenation, and dual-element isotope slopes (2.2–2.8) were distinctly different compared to dehalogenation mediated by corrinoids (4.6−7.0). Remarkably, ε_C/ε_Cl of PCE depended in addition on the corrinoid type: ε_C/ε_Cl values of 4.6 and 5.0 for vitamin B₁₂ and norvitamin B₁₂ were significantly different compared to values of 6.9 and 7.0 for norpseudovitamin B₁₂ and dicyanocobinamide. Our results therefore suggest mechanistic and/or kinetic differences in catalytic PCE dehalogenation by enzymes and different corrinoids, whereas such differences were not observed for TCE.