Geochemical data for aqueous, mine tailings, and sediment samples collected from the Big River and Meramec River drainage basins in southeastern Missouri are presented. The Big River drains historical lead, zinc, and barite mining districts, including the Old Lead Belt (OLB). Underground mining in the OLB resulted in large mine-waste chat piles and tailings impoundments that have released material laden with lead, zinc, and other trace elements to the Big River drainage basin. The Meramec River has also been affected by mining-related material transported by the Big River. Since the late 1980s, the U.S. Geological Survey (USGS) has been involved in investigations into the effects of mining on the Big River. The data presented here were generated as part of collaborations between the USGS Central Midwest Water Science Center, the USGS Mineral Resources Program, the U.S. Environmental Protection Agency, and the Missouri Department of Natural Resources. Flood deposit sediments were collected immediately after major flooding of the Big and Meramec Rivers in December 2016 and April 2017. Bed sediments and suspended sediments were collected by various methods during several field efforts from 2018 through 2022. Mine tailings were collected by coring on the former Federal mine tailings impoundment within St. Joe State Park in 2018. Concentrations of major and trace elements were determined for multiple particle size fractions of solid-phase samples, and multi-element analyses of deionized water leaches and sequential extractions were performed on select samples. Aqueous samples were collected from the Big River, tributaries, and mine and mine-waste seeps at near baseflow conditions during three different field efforts in 2018, 2019, and 2021. Aqueous samples were analyzed for anions and major and trace elements. Concentrations of major and trace elements in streambed and suspended sediments collected from the Big River drainage basin in 1988 and 1999 are also reported; these data were previously published in a USGS report but are provided here for convenient comparison.