AbstractTwist bilayer graphene (tBLG) with a small magic angle deviated from trivial stacking exhibits fantastic electronic properties. However, the growth of large‐area tBLG with precisely controlled twist angle remains a grand challenge due to the thermodynamically unfavorable nucleation. Here, a bi‐oriented step‐guided strategy is theoretically proposed for the nucleation and epitaxial growth of tBLG, where the twist angle can be predetermined by the orientations of adjacent steps owing to the covalent alignment between the steps and graphene zigzag edges. The presence of bi‐oriented steps can greatly reduce the free energy of the tBLG with matched twist angle, thus promoting the nucleation priority of tBLG. Importantly, it is shown that the 28 sets of bi‐oriented steps with twist angles of 1.5°–30° can be intentionally constructed via two‐step miscutting from bulk crystal of catalytic metals by exploring all potential combinations of bi‐steps on different epitaxial surfaces. The employment of either low‐temperature CVD growth with certain precursors or the high‐melting‐point metal substrates is suggested to against the reconstruction of bi‐oriented steps during growth. This work demonstrates an efficient scheme for the epitaxial growth of large‐area tBLG with pre‐designed twist angle, which can be potentially extended to the growth of other twist 2D materials.