Aircraft and pressure vessel components experience stresses that are negative biaxial or multiaxial in nature. Biaxiality is defined as the ratio of stress applied parallel and normal to the crack front. In recent years, many experimental studies have been conducted on fatigue crack growth (FCG) under various biaxial loading conditions. Biaxial loadings affect crack front stresses and strains, fatigue crack growth rate and direction, and crack tip plastic zone size and shape. Many of these studies have focused on positive biaxial loading cases. No conclusive study has been reported out yet that accurately quantifies the influence of negative biaxiality on fatigue crack growth behavior. Lacking validation, implementation on real life problems remains questionable. To ensure safe and optimum designs, it is necessary to better understand and quantify the effect of negative biaxial loading on fatigue crack behavior. This paper presents the results of a study to quantify the effect of biaxial load cases ranging from B = −0.5 to 1.0 on fatigue crack growth behavior. Also, a simplified approach is presented to incorporate the effect of biaxiality into da/dN curves generated from uniaxial loading using an analytical approach without conducting expensive biaxial crack growth testing. Sensitivity studies were performed with existing test data available for AA2014-T6 aluminum alloy. Detailed elastic-plastic finite element analyses were performed using the different stress ranges and stress ratios with various crack sizes and shapes on notched and unnotched geometries. Constant amplitude loads were applied for the current work and comparison studies were made between uniaxial and different biaxial loading cases. It was observed from the study that negative biaxiality has a very pronounced effect on the crack growth rate and direction for AA2014-T6 if the externally applied load equal to 30% of the yield strength as compared with 40% of externally applied load for steel alloy quoted in the literature.