Here, we combine an advanced synthesis of two-dimensional (2D) materials (MoSe2) having well-defined atomic edge configurations with ab initio and atomistic molecular dynamics (MD) simulations to study how atomic edges interact with polyethylene (HDPE) chains in a dilute solution assembly process. Our results reveal that Mo-terminated zigzag (Mo-ZZ) edges act as preferred nucleation sites and strongly interact with HDPE chains. The HDPE chains align in parallel with the Mo-ZZ edges and form arrays of lamellae that are perpendicular to the edges. Interestingly, atomic edge configurations are observed to dramatically change such interactions. The crystallization discrepancy at different edges was demonstrated on the same piece of MoSe2 with different types of edges. The ab initio and MD simulations between n-alkane (n = 5 and 25), a segment of HDPE, and MoSe2 suggest that the atomic structures of MoSe2 can affect their interactions with n-alkane chains. Following the Mo-ZZ edge preferred nucleation principle, controlled long-range alignment of HDPE lamellae can be realized by creating multilayer MoSe2 with parallel atomic steps. This research opens a pathway toward an atomic level understanding of polymer–2D nanomaterial interactions. It also bridges the gap between atomic-level and long-range mesoscopic structures and introduces a novel strategy for long-range structural control.