Native species in lakes commonly are affected by cultural eutrophication and introductions of nonnative species. The effects of these disturbances on benthic communities in large lakes have been understudied, despite the integral role that benthos play in maintaining habitat complexity and ecosystem processes. Lake Tahoe has experienced progressive eutrophication and introductions of nonnative species over the past several decades, but how its unique benthic communities have been affected is unclear. The density of Lake Tahoe's benthic fauna was compared between 1960s surveys and our recent (2008–2009) survey, and the association of zoobenthos with macrophytes was examined for contemporary and historical samples. The density of benthic invertebrates and the occurrence of macrophytes in benthic samples have declined dramatically since collections made in the 1960s. Lakewide densities of benthic invertebrate taxa endemic to Lake Tahoe have declined by 80 to 100%, and the community structure of benthic invertebrate assemblages has changed considerably. Several native benthic invertebrate taxa were closely associated with deepwater macrophytes in the 1960s, but contemporary invertebrate association with macrophytes could not be evaluated reliably because of the scarcity of macrophytes in contemporary samples. Declines in native benthic invertebrate density could be related to the loss of habitat and food resources previously provided by abundant deepwater macrophyte assemblages. In addition, establishment and increases in density of nonnative species that occurred after the benthic surveys of the 1960s probably have affected native benthic invertebrate communities. The observed declines in Lake Tahoe's native benthic invertebrate and macrophyte communities suggest that they are severely threatened.