In real engineering components and structures, many accidental failures are due to unexpected or additional loadings, such as additional bending or torsion, etc. Therefore, it has attracted more research attentions to study the mechanical behavior of materials under complex loading conditions. Two typical structural materials are studied and compared in this paper: AISI 303 stainless steel and 6060-T5 Aluminum alloy. The objective is to study the effects of multiaxial loading paths on the crack initiation and orientation of the two materials studied. Fatigue tests were conducted in a biaxial testing machine. Fractographic analyses of the fracture surface were carried out by optical microscope and SEM approaches. In addition to the experimental studies, theoretical predictions of the damage plane were made using critical plane approaches. Comparisons of the predicted orientation of the damage plane with the experimental observations are shown. The applicability of the multiaxial fatigue criteria for the two materials is discussed. It was shown that the two materials studied have different crack orientations under the same loading path. This observation appears to show that the applicability of the fatigue models is dependent on the material type and multiaxial microstructure characteristics.