Colonies of Herring (Larus argentatus) and/or Ring-billed Gulls (L. delawarensis) on Lake Ontario and the upper St. Lawrence River were searched annually, 1981–2018, for nesting Great Black-backed Gulls (L. marinus). Great Black-backed Gulls nested at nine sites where both Herring and Ring-billed Gulls nested, at seven sites with only Herring Gulls, and at one site where they nested solitarily. Nests per site ranged from 1–21 on Lake Ontario and 1–5 on the St. Lawrence River. On Lake Ontario, nest numbers increased from six nests in 1981 to 51 nests in 2001 (+ 11.3%/yr), then declined to zero nests in 2008, where they have remained ever since. The decline in nesting Great Black-backed Gulls was due primarily to mortality from Type E botulism that affected that species to a greater degree than other gull species, probably because of their superior ability to dominate and scavenge toxin-laden carrion. Temporal changes in routes and efficiency of botulinum toxin transfer likely explain why Great Black-back Gulls were initially able to colonize Lake Ontario, but have undergone extirpation in recent times. Our results illustrate how changes in disease prevalence in the Great Lakes can degrade environmental quality to the extent that some species simply cannot persist.