In-situ compact tension tests on binary lamellar titanium aluminide (TiAl) possessing the colony "polycrystalline" microstructure illustrate a range of damage phenomena and toughening mechanisms including crack nucleation across colony boundaries, plastic deformation of bridging ligaments, and multiple cracking within colonies. Here, the effects of relative lamellae misorientation and offsets between neighboring colonies on crack growth are investigated computationally through an idealized microstructure of multiple colonies. Within each colony, the brittle Ti3Al lamellae are represented as parallel planes of comparatively low toughness embedded in a matrix of ductile TiAl lamellae that are collectively modeled as an elastic-viscoplastic solid with higher fracture toughness. Plane strain calculations of crack growth are carried out on a compact tension geometry. The calculations are in good qualitative agreement with the in-situ observations, capturing many features of crack growth such as multiple microcrack nucleation and plastic deformation of residual ligaments. Experiments and numerical analyses show that changes in lamellar orientation and alignment across a colony boundary can contribute significantly to the fracture resistance. The numerical results demonstrate that the fracture resistance of these alloys is determined by an intricate interplay between matrix ductility, Ti3Al and TiAl fracture toughnesses, and colony boundary toughness. This suggests the possibility of computationally-guided material optimization through microstructural control of these material properties.