Turkey astrovirus type-2 (TAstV-2), turkey rotavirus (TRotV), and turkey reovirus (TReoV) have been implicated as possible causes of enteric diseases and poor production in turkeys; however, numerous studies with each individual virus have failed to reproduce the disease as observed in the field. Therefore, in this study we evaluated the pathogenesis of all possible combinations of one, two, or three viruses in comparison to sham inoculates in 3-day-old turkey poults. Body weights were recorded at 2, 4, 7, 10, and 14 days postinoculation (PI) and were decreased in virus-infected turkeys throughout the experiment as compared to sham inoculates. Although not significantly different from the other virus-exposed groups, the poults exposed to all three viruses had the lowest body weights throughout the experiment. Clinical signs, including huddling, diarrhea, and agitation, were only observed in groups exposed to TAstV-2 and/or TRotV. At 4 days PI, birds from each treatment group were necropsied, and pale intestines with watery contents and undigested feed were observed in the groups that were exposed to TRotV TReoV or TRotV TAstV-2 and the group exposed to all three viruses. Minimal microscopic lesions were observed in the intestines of turkeys infected with TAstV-2, TReoV, or a combination of both. In the turkeys infected with TRotV, either alone or in combination with other viruses, mild microscopic lesions were found in all sections of the small intestine and viral antigen was identified by immunohistochemical staining in mature enterocytes. No or very mild lesions were observed in other organs with the exception of the bursa of Fabricius, where mild to severe atrophy was observed in all virus-infected poults examined. Cloacal shedding of TAstV-2 and TRotV was evaluated by reverse-transcription PCR testing of cloacal swabs and minimal differences were observed among the treatment groups.