Background <p>Straw return is one of the most promising agricultural practices to mitigate climate change by enhancing soil carbon sequestration. Microbial-induced decomposition processes are fundamental for soil carbon persistence, but the enzymatic mechanisms underlying SOC accumulation remain unclear.</p> Methods <p>Here, we conducted a global meta-analysis of 127 observations from 43 field studies to quantify the effect of straw return on soil cellulase activity and its associations with soil organic carbon (SOC) worldwide.</p> Results <p>On average, straw return increased cellulase activity by 22.5%, primarily driven by straw management strategies (i.e., straw mulch had stronger effects than straw incorporation). Straw return also increased SOC by 18.9% and soil microbial biomass carbon (MBC) by 27.1%. Straw return effects on SOC and MBC were indirectly modulated by cellulase activity: MAP, soil pH, NDS, and WSC influenced cellulase responses, which in turn drove changes in SOC and MBC. The lowest SOC response at MAP ~ 900 mm, soil pH ~ 6.5, NDS ~ 22, and WSC ~ 6 corresponded with inhibited cellulase activity.</p> Conclusions <p>Our results demonstrate that straw return exerts a general impact on carbon-degrading enzymes (e.g., cellulase), with critical implications for SOC cycling under global change.</p>