A strain-based criterion is presented in this paper to investigate mixed-mode I/II fracture behavior in orthotropic materials. The maximum principal strain component, in the vicinity of a crack existing in an orthotropic medium, is formulated considering the T-stress effect as well as the singular terms. The criterion predicts the onset of mixed-mode I/II fracture when the maximum principal strain reaches its critical value. The role of T-stress, calculated for an orthotropic domain, in the mixed-mode I/II fracture toughness assessment is explored theoretically. Along with other criteria, the accuracy of the proposed criterion is evaluated by predicting the fracture test data in the literature for wood species and laminated composites. The developed criterion is shown to be superior to other criteria in predicting the onset of mixed-mode I/II fracture in orthotropic materials.