Organic matter (OM) in rivers, influenced by natural and anthropogenic events, plays a critical role in regulating methylmercury (MeHg) dynamics. This study investigated the spatial-temporal patterns of MeHg and OM in the Yellow River, through collecting water and sediment samples within the dry and wet seasons and human-induced water-sediment regulation scheme (WSRS) event. During the wet season, the river water was characterized by terrigenous OM, high unfiltered MeHg (UMeHg) concentration (206 ± 83.6 pg/L), and a low UMeHg percentage in unfiltered total Hg (UTHg) (UMeHg/UTHg = 0.37 ± 0.18 %). These findings may suggest that MeHg in the wet season was likely produced in the catchment and imported into the river. In contrast, autochthonous OM predominated during the dry season, probably enhancing in situ MeHg production (UMeHg/UTHg = 1.01 ± 0.50 %), although UMeHg concentration was lower (81.8 ± 25.5 pg/L) due to obviously reduced external inputs. The WSRS dramatically increased water MeHg contents (589 ± 116 pg/L) and UMeHg/UTHg ratios (0.78 ± 0.16 %) probably through direct inputs of upstream reservoirs' MeHg and resuspension of downstream sediments. Exploring the effects of OM on sediment MeHg sources suggested that MeHg in the wet season primarily originated from watershed soil inputs, while in the dry season, it mainly resulted from in situ Hg methylation. However, extremely low total Hg (THg) and MeHg/THg (0.02-0.35 %) indicated that sediment MeHg production may be of minor importance in the Yellow River.