The planning of multi-branch cable harness layouts holds significant practical importance in aircraft industrial contexts, yet it has received limited attention in prior research. This study aims to address the matter concerning the significance of managing multiple constraints and preventing loops. It formulates the problem as an optimization problem in 3D free-form space and resolves it using an extended A* path planning approach in combination with the ant colony optimization algorithm. Initially, a feasible search space for wiring is established through the repair and simplification of the input CAD model. Subsequently, the topology of a multi-branched wiring harness is identified, taking into account industrial requirements related to cable physics, turning, support, bundling, and electromagnetic compatibility constraints. Specifically, the disassembly or merging of branches and loops is employed to avoid wire loops. Ultimately, we propose an A*–ant colony optimization algorithm (A*-ACO) with an enhanced heuristic function for neighboring points, incorporating a concentration increment model. Experimental tests illustrate the effectiveness of this approach in minimizing wire loops and reducing the total cable layout cost, considering factors such as length, bundling, and turning costs. It results in a reduction of 67.0%, 68.5%, and 51.1% compared to A*, ACO, and manual wiring methods, respectively.