This work aims to investigate the complex fracture behavior of a large opening box girder (LOBG) using three-dimensional (3D) finite element method (FEM). A numerical model is developed to simulate the fracture of LOBG under individually or jointly applied torsion and bending loads. The crack damage is introduced into the side plate and bottom plate of LOBG. The influencing factors such as crack angles, crack locations, and load types are emphatically discussed. Additionally, the crack growth angles are also predicted during the analysis. The results present that the large opening can generate significant effects on the crack growth of the side plate crack (SPC) and the bottom plate crack (BPC). Under the condition of torsion or hogging, SPC grows more easily than BPC, while BPC is relatively prone to grow under sagging condition. Compared with the torsion condition, the initial crack angle can significantly reduce the stress intensity factor (SIF) under the bending condition. Furthermore, the cracks that gradually approach transverse frames are also more likely to induce mode I fracture under torsion conditions. These findings from the present study can reveal insights for a better understanding of fracture behavior for LOBG.