This article presents the fatigue life prediction in a cruciform specimen of 2024-T351 aluminum alloy subjected to biaxial FALSTAFF loading. An energyand slip-based multiscale damage criterion is developed to capture the fatigue crack formation in crystalline metallic materials. In these materials, there are two stages in crack initiation: nucleation of micro cracks and coalescence of micro cracks into major cracks. In the first stage, micro cracks generate from intermetallic particles and extend into surrounding grains. For the FCC crystalline structure, fatigue damage increments in four dependent slip planes are calculated and accumulated to measure micro crack. In the second stage, the micro cracks grow and coalesce into major cracks. Subsequently, a meso-statistical volume element model is developed to represent the microstructure of the material. Finally, a root mean square method is introduced to take into account FALSTAFF loading. Using the root mean square (RMS) method, the loading history for tests is analyzed to determine the RMS maximum and minimum stresses. The multiscale damage criterion, statistical volume element and RMS method were validated using previously conducted fatigue tests on cruciform samples. The fatigue life and crack direction predicted using the developed model correlate well with the experiments.