Hypereutrophic Upper Klamath Lake has been studied for almost 50 years to evaluate the nature, cause, and effects of its very productive waters. Mitigation of undesirable effects of massive cyanobacterial blooms requires understanding their modern causes as well as their history. Knowledge of the pre-settlement natural limnology of this system can provide guidelines for lake restoration and management of land and water use strategies to maximize the benefits of this aquatic resource. This investigation uses a paleolimnological approach to document the nature and chronology of limnological and biological changes in Upper Klamath Lake for the past 200 years, covering the time when the lake was first described until today. A 45-cm gravity core, dated by 210Pb and diatom correlations, was analyzed for diatoms, pollen, akinetes (resting spores) of the cyanobacterium Aphanizomenon flos-aquae, reworked tephra shards, and sediment magnetic characteristics. Pollen profiles show little vegetation change during this time. In contrast, diatoms indicative of increased nutrient fluxes (P and Si) increase moderately, coinciding with the settlement of the region by Euro-Americans. Numerous settlement activities, including draining of lake-margin marshes, upstream agriculture and timber harvest, road construction, and boat traffic, may have affected the lake. Magnetic properties and reworked tephra suggest riparian changes throughout the basin and increased lithogenic sediment delivery to the lake, especially after 1920 when the marshes near the mouth of the Williamson River were drained and converted to agricultural and pasture land. Drainage and channelization also decreased the ability of the marshes to function as traps and filters for upstream water and sediments. Akinetes of Aphanizomenon flos-aquae record progressive eutrophication of Upper Klamath Lake beginning in the 20th century and particularly after 1920 when lake-margin marsh reclamation more than doubled. The coincidence of limnological changes and human activities following European settlement suggests a major impact on the Upper Klamath Lake ecosystem, although ascribing specific limnological changes to specific human activities is difficult.