Downstream　water　supply　disruption　accidents　commonly　occur　in　the　large-scale　cascade　open-channel　dispatching　system,　endangering　dispatch　safety.　The　emergency　reaction　requires　active　drainage　water　volume　and　cost　control.　This　research　introduces　a　simulation　optimization　emergency　response　optimization　control　model　using　enhanced　one-dimensional　hydrodynamic　simulation　and　multiobjective　particle　swarm　optimization　(MOPSO),　verifying　the　Gangtou　Gate-Beijuma　Gate　section　(GB　section)　of　the　Middle　Route　Project　of　South-to-North　Water　Diversion　in　China.　In　the　downstream　large-flow　water　supply　interruption　scenario,　we　explore　regulation　possibilities　for　optimization　elements,　including　drainage　water　volume,　regulation　frequency,　and　regulation　interval.　The　optimization　of　the　drainage　water　volume　significantly　raises　the　regulation　frequency　of　the　sluice　when　the　regulation　interval　is　fixed.　The　drainage　water　volume　can　be　balanced　and　optimized,　and　the　frequency　of　sluice　control　can　be　decreased,　by　increasing　the　regulation　interval.　The　emergency　response　optimization　control　model　may　minimize　the　regulation　frequency　by　80%　and　the　drainage　water　volume　by　32.6%　compared　with　the　benchmark　scheduling　approach　in　emergencies.　The　model　provides　superior　economic　and　applicable　effects　for　emergency　reactions　to　the　downstream　water　supply　disruption,　with　similar　advantages　feasible　for　other　cascade　open-channel　scheduling　systems.　　©　2023　American　Society　of　Civil　Engineers.