Historically, Lake Okeechobee was thought to be impaired only by phosphorus, focusing efforts on reducing agricultural runoff. However, new comprehensive sampling across the Lake Okeechobee Waterway and its connected estuaries shows that toxic algal blooms also are driven by rising nitrogen levels from human waste and urban runoff. Increased nitrogen, worsened by extreme rainfall, significantly fuels bloom severity. Findings underscore the need for integrated nutrient management and improved wastewater treatment to protect the lake and its estuaries.