Upper Klamath Lake, located in southern Oregon, is a hypereutrophic lake where cyanobacterial blooms, dominated by Aphanizomenon flos-aquae (AFA), occur every summer. The decay of excess biomass after AFA senescence leads to problematic water quality conditions including high pH ( > 9) and anoxia. Water samples from the photic zone and bottom of the water column, and the flocculation layer of the bottom sediments were collected weekly at four sites within Upper Klamath Lake, Oregon during summer 2016. This data release reports the chemical and microbiological analysis of these samples.