Invasive species have had major impacts on the Great Lakes. This is especially true of exotic dreissenid mussels which are associated with decreased abundance of native macroinvertebrates and changes in food availability for fish. Beginning in 2001, we added a benthic macroinvertebrate survey to the USGS-Great Lakes Science Center's annual fall prey fish assessment of Lake Huron to monitor abundance of macrobenthos. Mean abundance of Diporeia, the most abundant benthic taxon in Lake Huron reported by previous investigators, declined greatly between 2001 and 2007. Diporeia was virtually absent at 27-m sites by 2001, decreased and was lost completely from 46-m depths by 2006, but remained present at reduced densities at 73-m sites. Dreissenids in our samples were almost entirely quagga mussels Dreissena bugensis. Zebra mussels Dreissena polymorpha were virtually absent from our samples, suggesting that they were confined to nearshore areas shallower than we sampled. Loss of Diporeia at individual sites was associated with arrival of quagga mussels, even when mussel densities were low. Quagga mussel density peaked during 2002, then decreased thereafter. During the study quagga mussels became established at most 46-m sites, but remained rare at 73-m sites. Length frequency distributions suggest that initial widespread recruitment may have occurred during 2001–2002. Like other Great Lakes, Lake Huron quagga mussels were associated with decreased abundance of native taxa, but negative effects occurred even though dreissenid densities were much lower. Dreissenid effects may extend well into deep oligotrophic habitats of Lake Huron.