The microbial priming effect - the decomposition of soil organic carbon (SOC) induced by plant inputs - has long been considered an important driver of SOC dynamics, yet we have limited understanding about the direction, intensitiy, and drivers of priming across ecosystem types and biomes. This gap hinders our ability to predict how shifts in litter inputs under global change can affect climate feedbacks. Here, we synthesized 18,919 observations of CO2 effluxes in 802 soils across the globe to test the relative effects (i.e., log response ratio; RR) of litter additions on native SOC decomposition, and identified the dominant environmental drivers in natural ecosystems and agricultural lands. Globally, litter additions enhanced native SOC decomposition (RR = 0.35, 95% CI: 0.32 ~ 0.38), with greater priming effects occurring with decreasing latitude, and more in agricultural soils (RR = 0.43) than in uncultivated soils (RR = 0.28). In natural ecosystems, soil pH and microbial community composition (e.g., bacteria:fungi ratio) were the best predictors of priming, with greater effects occurring in acidic, bacterial-dominated, sandy soils. In contrast, substrate properties of plant litter and soils were the most important drivers of priming in agricultural systems, as soils with high C:N ratio and those receiving large inputs of low quality litter had the highest priming effects. Collectively, our results suggest that while different factors may control priming effects, the ubquitious nature of priming means that alterations of litter quality and quantity owing to global changes will likely have consequences for global C cycling and climate forcing.