Major threats to aquatic systems such as shallow lakes can include declining water quality, the loss of macrophyte beds, and the occurrence of harmful algal blooms. Often, these changes go unnoticed until a shift from a clear, oligotrophic system dominated by macrophyte beds to a turbid, eutrophic system dominated by phytoplankton and associated harmful algal blooms has occurred. Lake Mattamuskeet, which mostly lies within the boundary of Mattamuskeet National Wildlife Refuge, North Carolina, is a shallow lake that has recently experienced a reduction in water clarity and macrophyte beds, also referred to as submerged aquatic vegetation (SAV), and an increase in nutrients, phytoplankton, harmful algal blooms, and cyanotoxin production. At Lake Mattamuskeet, SAV coverage and water clarity declined between the 1980s and 2015. During the same time, significantly increasing trends in nitrogen, phosphorus, turbidity, suspended sediments, chlorophyll a, and pH occurred. Current water-quality conditions (2012–2015) are not conducive to SAV survival and, in some cases, do not meet North Carolina water-quality standards for the protection of aquatic life. Water clarity declines appear to predate the SAV die-offs on the east side. Moving forward, SAV will serve as a primary indicator for lake health; and lake monitoring, research, and management efforts will focus on the restoration of aquatic grasses and water quality at Lake Mattamuskeet.