<p>Directed hydrogen isotope exchange strategies have become an essential tool for accessing isotopically labelled organic scaffolds and interrogating the mechanisms of transition metal-catalysed C–H activation. However, the rationale behind deuterium source selection remains largely absent from the literature; an oversight that directly affects mechanistic interrogation strategies and hinders the development of new deuteration methodologies. Here we explore the influence of the deuterium source in base-assisted site-selective C–H deuteration reactions across a broad range of substrates using cobalt catalysis. We employ a synergistic combination of experimental studies and multivariable linear regression models based on proposed catalytic intermediates. Our findings demonstrate that the deuterium source can directly alter the operative mechanism, leading to distinct reaction pathways under different conditions. These results highlight previously overlooked complexity in hydrogen isotope exchange reactions and provide an example of how data-driven mechanistic analysis can expose subtle, reagent-dependent mechanistic shifts in catalytic behaviour.</p><p></p>