Plant roots are the primary source of soil organic carbon (C) and critically support the growth and activities of microbes in the rhizosphere. Climate change factors may, however, modify root-microbial interactions and impact C dynamics in the rhizosphere. Yet, the direction and magnitude of interactive climate change effects, as well as the underlying mechanisms, remain unclear. Here we show evidence from a field experiment demonstrating that warming and precipitation changes strengthen root controls over litter decomposition in a semi-arid grassland. While warming and precipitation reduction suppressed microbial decomposition of root litter regardless of the root presence, precipitation increase stimulated litter decomposition only in the absence of roots, suggesting that plant competition for water constraints the activities of saprophytic microbes. Root presence increased microbial biomass but reduced microbial activities such as respiration, C cycling enzymes and litter decomposition, indicating that roots exert differential effects on microbes through altering C or water availability. In addition, nitrogen (N) input significantly reduced microbial biomass and microbial activities (respiration). Together, these results showed that alterations in soil moisture induced by climate change drivers critically modulate root controls over microbial decomposition in soil. Our findings suggest that warming-enhanced plant water utilization, combined with N-induced suppression of microbes, may provide a unique mechanism through which moderate increases in precipitation, warming and N input interactively suppress microbial decomposition, thereby facilitating short-term soil C sequestration in the arid and semi-arid grasslands.