Bulk molybdenum carbides catalyze the Fischer-Tropsch (FT) reaction but display low selectivity to liquid hydrocarbons. Understanding which structural features of Mo carbide-based catalysts correlate with a selectivity to C5+ products requires detailed structure-performance studies. Here, we investigate the effect of Mo vacancies (VMo) on the FT performance of the two-dimensional (2D) i-MXene Mo4/3CT x , where T x are the surface passivating groups. We show that the initially ordered VMo sites, constituting ca. one-third of all Mo sites in Mo4/3CT x , undergo clustering already at 250 degrees C under H2. Following VMo clustering, lattice carbon is released as CH4 and CO, creating carbon vacancies (VC), which also form in Mo4/3CT x under FT conditions at 330 degrees C. The presence of VC sites is associated with a high selectivity towards methane and C2-C4 alkanes and a reduced selectivity for higher, C5+, alkanes. Mo4/3CT x converts CO at a rate of ca. 60-80 mmolCO (gcat h)-1, which is comparable to that of the T x -free 2D-Mo2C and 2D-Mo2C1-x reference catalysts that only contain a Mo+2 (carbidic) electronic state. However, post-FT analysis of Mo4/3CT x shows that it contains Mo+2, Mo+4, and Mo+5 states, possibly because oxygen atoms populate the VC sites and do not block the Mo+2 active sites at the surface. Mo4/3CT x undergoes a phase transition to cubic alpha-MoC1-x at 400 degrees C under H2, which leads to a continuous deactivation under FT conditions, suggesting, more generally, that pretreatment protocols for MXenes should be carefully optimized to unlock their potential in thermal catalysis.