The present work discusses the evolution of grain boundary structure during thermomechanical processing and its effect on sensitization behavior in a nickel-based superalloy. Alloy 600 was deformed to varied degrees of strain (4–25%) using hot rolling followed by annealing at 1000 °C for 10 min followed by water quenching. Structure of the grain boundary was analyzed with reference to various parameters, such as grain boundary character distribution, twin-related domains, misorientation, and triple junction distribution. Each thermomechanically processed sample was heat-treated at 650 °C for 24 h before studying its sensitization behavior. The effect of structure of the grain boundary on sensitization was assessed through double loop electrochemical potentiokinetic reactivation test and measured in terms of degree of sensitization (DOS). DOS was found to be in a direct relation with the fraction of random high-angle grain boundaries and their connectivity, while it was inversely related to the fraction of low-Σ coincidence site lattice boundaries and special triple junctions. Residual strain and the fraction of low-angle grain boundaries were found to be weakly related to DOS. We show that a simple parameter can be used to predict the combined effect of all these factors on sensitization behavior. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.