The present work reports on a detailed study of the effect of support chemical composition and reaction temperature on the mechanism of the water–gas shift (WGS) reaction over supported-Pt catalysts. The effect of the same parameters on the chemical composition and surface concentration of active reaction intermediates was also determined for the first time, information that allowed elucidating also the site location of these intermediates, e.g., support versus metal or support–metal interface. The above-mentioned mechanistic information was rigorously provided by the application of steady-state isotopic transient kinetic analysis (SSTIKA) experiments coupled with mass spectrometry (MS) and DRIFTS techniques, and by other transient isotopic experiments designed. It was found that on Pt/CeO2 a switch of the WGS reaction mechanism from “redox” to a combination of redox and “associative formate with −OH group regeneration” is obtained after increasing the reaction temperature from 473 to 573 K. On the other hand, only the redox mechanism operates on Pt/TiO2 of similar Pt mean particle size. Modification of titania support by the deposition of small crystallites of ceria in its pore structure enhanced significantly the activity of WGS at T > 573 K compared to Pt/TiO2, whereas the operated mechanism resembles that occurring on Pt/CeO2. In all supported-Pt catalysts investigated, the concentration of active “carbon-containing” intermediates found in the “carbon-path” was significantly lower than that found for the “hydrogen-containing” intermediates present in the “hydrogen-path”, the latter being labile OH and H species formed on the support, and which were found to depend on the support chemical composition and reaction temperature. This study provides new important fundamental knowledge on the mechanism of WGS over practical supported metal catalysts which can be used for a better WGS catalyst design.