Rotavirus is a clinically significant pathogen and is the causative agent of life-threatening gastroenteritis in many young humans and animals. The interaction between the rotavirus spike-protein (VP8*) and cell surface glycoconjugates facilitate virus initial cell attachment and subsequent cell entry. Here, we report the first observation of significant structural rearrangement of VP8* from human and animal rotavirus strains upon glycan receptor binding. The structural adaptability of rotavirus VP8* delivers important insights into how human and animal rotaviruses utilize the wider range of cellular glycans identified as VP8* binding partners. VP8* ability to accommodate multiple glycans, provide important insight into the mechanism of infection of rotaviruses. Collectively, our studies on rotaviruses with atypical genetic makeup provide information expected to be critical for understanding the mechanisms of animal rotavirus gene emergence in humans and support the implementation of epidemiologic surveillance of animal reservoirs as well as future vaccination schemes. In addition, our findings could be exploited for inhibiting the rotavirus infection at its early stage and better therapeutics can be designed and developed by considering the flexibility in its carbohydrate binding precinct.