Designing organic semiconductor thin films with controlled molecular orientation is crucial for enhancing device performance. In this study, we tackle this challenge by analyzing the mechanism underlying molecular orientation from a molecular design perspective. We synthesize two types of p-type semicrystalline polymers, PPDT2FBT-2C and PPDT2FBT-5C, which differ in their side-chain branch points. PPDT2FBT-5C, with increased distance between the main chain and the branching point, promotes strong preaggregation in solution, leading to a shift in dominant orientation from face-on to edge-on. Molecular dynamics simulations provide insights into the mechanism of orientation change in thin films. For highly aggregated PPDT2FBT-5C polymers, the length of the π−π packing cluster is sufficiently large, increasing the surface area of the alkyl side chains within the cluster. This facilitates polymer interaction with the substrate and enables stacking in the edge-on orientation. The distinct orientations observed in PPDT2FBT-2C and PPDT2FBT-5C correlate well with the electrical properties of horizontal and vertical organic field-effect transistors and solar cells, suggesting a strategy for developing tailored materials with specific molecular alignment to optimize various optoelectronic devices.