Recent changes in Lake Michigan's lower trophic levels were hypothesized to have influenced the diet of omnivorous Mysis diluviana. In this study, the stomach contents of Mysis were examined from juvenile and adults collected monthly (April–October) from a 110-m bottom depth site to describe their seasonal diet in Lake Michigan during 2010. Diatoms were the most common prey item ingested, followed by calanoid copepods, and chrysophytes. Dreissenid veligers were documented in mysid diets for the first time in the Great Lakes, and Cercopagis pengoi were not only consumed but even preferred by adults in summer. Diet proportions by weight were dominated by calanoids, although diets showed a marked shift toward cladocerans in autumn. Juvenile and adult Mysis selected primarily for cladoceran prey but also selected for some calanoid copepod taxa. Comparing available Mysis diet data from 1985 to 2010 indicated generally fewer cladocerans and rotifers per gut and less consistent differences in copepods and Peridinium consumed. The seasonal composition of phyto- and zooplankton prey documented herein should be useful to those seeking to understand the trophic role of Mysis in offshore food webs, but caution should be expressed when generalizing similarities in Mysis diets across other lakes because Lake Michigan's population seems relatively more herbivorous.