Recent observations of superconductivity in twisted bilayer WSe₂ (tWSe₂) have motivated theoretical proposals for unconventional pairing mechanisms. A central question is whether band topology plays an essential role in the system's correlation physics. In this letter, we develop a first-principles-based description of the top moiré valence bands in tWSe₂. Using density functional theory (DFT) calculations, we identify the bands in the relevant range of twist angles to be topologically non-trivial, with the top valence bands carrying Chern numbers C=(+1,+1) for the K valley. In order to treat the strong correlation physics, we construct compact molecular orbitals directly from the DFT wave functions through a partial Wannierization procedure and with the guidance of spinful C_3z symmetry representations. This yields a localized f orbital together with a complementary topological c orbital, allowing us to extract hopping and hybridization amplitudes from first principles. The resulting parameters provide an ab initio benchmark for the effective Hamiltonian. Our work establishes a foundation for understanding superconductivity in moiré TMDs and highlights tWSe₂ as a promising platform for exploring topological superconductivity.