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Mineral particles provide reactive sites for organic carbon (C) to bind in soil; this ‘mineral-associated organic matter’ (MAOM) may persist for centuries to millennia or cycle rapidly in minutes to days. The conditions and processes that influence short and long-term cycling of MAOM are poorly constrained. Soil moisture is one key control on organic matter cycling in soil, and projected shifts in moisture regimes towards more intense rainfall and prolonged drought under climate change may alter MAOM formation and cycling. Here, in a 3-week laboratory incubation study, we evaluated how two contrasting moisture regimes affected the formation and cycling of 13C-labeled MAOM from two mineralogically-distinct soil types. Repeated wet-dry cycling (between 3% and 60% of water-holding capacity) enhanced the formation of 13C-MAOM relative to constant moisture conditions. The two soil types differed in rates of MAOM formation and the sensitivity of newly-formed and pre-existing MAOM to subsequent priming in the presence of simulated exudates (glucose and/or oxalic acid). Wet-dry cycling enhanced the decomposition of newly-formed MAOM and it further accelerated the potential priming of pre-existing MAOM. Therefore, while repeated cycles between drought-like and “optimal” moisture conditions may promote the formation of MAOM, they may also undermine the stability of pre-existing MAOM and limit opportunities for new C inputs to enter more persistent forms.