The effects of nonproportional biaxial loading paths on ductile fracture initiation toughness are studied in this article. To this end, the growth of a cylindrical void (hole) located in front of a mode I plane strain crack has been studied using large-deformation finite element analysis. A specific microstructural feature of a steel alloy was thoroughly studied by having a single void positioned at a fixed distance from the crack tip and void that was equal to 10 times the diameter of the void. In particular, the nonproportional biaxial loading path effects on the crack tip blunting, void growth, ligament reduction, and near-tip stress fields are investigated computationally. Under small-scale yielding conditions, one proportional loading and two nonproportional loading paths are applied to the modified boundary layer models, covering both low-constraint (negative T-stress) and high-constraint (positive T-stress) crack tip conditions. We have observed that the nonproportional load paths have a marked effect on the void growth, crack tip blunting, and the resulting ligament reduction. By applying the simple criteria for the coalescence of the crack tip and void, the ductile fracture initiation toughness is estimated. It is shown that the ductile fracture toughness is dependent on loading paths and constraint conditions (the T-stress ratios). Compared with the proportional biaxial loading case, different load sequences of the biaxial loads will result in either an increase or a decrease the fracture initiation toughness. This effect is particularly significant for specimen geometry with low-constraint conditions (i.e., negative T-stress ratios). Results from this study are of relevance to ductile fracture assessment of components or structures, such as pressure vessels that operate under nonproportional biaxial loading conditions.