Drainage poses a major threat to the tremendous soil organic carbon (SOC) reservoir in wetlands. However, drainage-induced carbon loss may be mitigated by the accumulation of mineral-associated organic carbon (MAOC) via both microbial processes and iron (Fe)-organic matter (especially lignin) interactions, which remains under-investigated in wetlands. Here using a novel analytical approach, we quantitatively examined the response of MAOC to drainage and the driving mechanisms in four distinct wetlands. Contrary to the prevailing assumption, MAOC consisted a significant fraction (7%∼91%) of wetland SOC, and increased with mineral-bound (microbial-dominated) sugars, but decreased with Fe-bound lignin phenols in SOC assessed after removal of reactive soil minerals. Furthermore, mineral-bound sugars increased with clay and reactive aluminum instead of Fe, and overrode Fe-bound lignin regarding contribution to MAOC after long-term drainage. These results indicate that microbial processes leading to microbial sugars accumulation played a prominent role in wetland MAOC accrual after long-term drainage, especially in soils rich in reactive Al and clay. Our study highlights the prevalent yet under-investigated microbial regulation on MAOC accrual in wetlands during long-term drainage. Given the large stock and persistence of MAOC in wetlands, its increase may partly compensate for particulate organic carbon loss during drainage, and may underpin wetland SOC stabilization in the long term.