Monitoring changes in diets of fish is essential to understanding how food web dynamics respond to changes in native prey abundances. In the Great Lakes, Diporeia, a benthic macroinvertebrate and primary food of native benthivores, declined following the introduction of invasive Dreissena mussels and these changes were reflected in fish diets. We examined the diets of deepwater sculpin Myoxocephalus thompsonii collected in bottom trawls during 2010–2014 in the main basin of Lake Huron, and compared these results to an earlier diet study (2003–2005) to assess if their diets have continued to change after a prolonged period of Dreissena mussel invasion and declined Diporeia densities. Diporeia, Mysis, Bythotrephes, and Chironomidae were consumed regularly and other diet items included ostracods, copepods, sphaerid clams, and fish eggs. The prey-specific index of relative importance calculated for each prey group indicated that Mysis importance increased at shallow (≤55 m) and mid (64–73 m) depths, while Diporeia importance increased offshore (≥82 m). The average number of Diporeia consumed per fish increased by 10.0% and Mysis decreased by 7.5%, while the frequency of occurrence of Diporeia and Mysis remained comparable between time periods. The weight of adult deepwater sculpin (80 mm and 100 mm TL bins) increased between time periods; however, the change in weight was only significant for the 80 mm TL group (p < 0.01). Given the historical importance of Diporeia in the Great Lakes, the examination of deepwater sculpin diets provides unique insight into the trophic dynamics of the benthic community in Lake Huron.