© 2014 AIP Publishing LLC. We have used a multi-scale physics-based model to predict how the grain size and different grain boundary morphologies of polycrystalline graphene will impact the performance metrics of graphene field-effect transistors. We show that polycrystallinity has a negative impact on the transconductance, which translates to a severe degradation of the maximum and cutoff frequencies. On the other hand, polycrystallinity has a positive impact on current saturation, and a negligible effect on the intrinsic gain. These results reveal the complex role played by graphene grain boundaries and can be used to guide the further development and optimization of graphene-based electronic devices.