Proximity-induced phenomena in van der Waals heterostructures have emerged as a platform to tailor the electronic, spin, optical, and topological properties in two-dimensional materials. A crucial degree of freedom, which has only recently been recognized, is the relative twist angle between the monolayers. While partial results exist in the literature, we present here a comprehensive first-principles-based investigation of the twist-angle-dependent proximity spin-orbit coupling (SOC) in graphene in contact with, or encapsulated by, monolayer transition metal dichalcogenides (TMDCs) , , , and . Crucially, our commensurate supercells comprise monolayers with strains of less than 2.5%, minimizing band-offset artifacts. We confirm earlier DFT results that for Mo-based TMDCs the proximity valley–Zeeman SOC exhibits a maximum at around and vanishes at for symmetry reasons. Although such a maximum was also predicted by tight-binding simulations for W-based TMDCs, we find an almost linear decrease of proximity valley–Zeeman SOC in graphene/ and graphene/ when twisting from to . We also refine previous DFT simulations and show that the induced Rashba SOC is rather insensitive to twisting, while acquiring a nonzero Rashba phase angle which measures the deviation of the electron spin from in-plane transverse direction to the momentum, for twist angles different from and . The Rashba phase angle varies from to , with the largest variation () found for at a twist angle of . This finding contradicts earlier tight-binding predictions that the Rashba angle can be in the studied systems. In addition, we study the influence of a transverse electric field, vertical and lateral shifts, and TMDC encapsulation on the proximity SOC for selected twist angles. Within our investigated electric field limits of V/nm, mainly the Rashba SOC can be tuned by about 50%. The interlayer distance provides a giant tunability, since the proximity-induced SOC can be increased by a factor of 2–3, when reducing the distance by only about 10%. When encapsulating graphene between two TMDCs, both twist angles are important to control the interference of the individual proximity-induced SOCs, allowing to precisely tailor the proximity-induced valley-Zeeman SOC in graphene, while the Rashba SOC becomes suppressed. Finally, based on our effective Hamiltonians with fitted parameters to low-energy ab initio band structures, we calculate experimentally measurable quantities such as spin lifetime anisotropy and charge-to-spin conversion efficiencies. The spin lifetime anisotropy—being the ratio between out-of-plane and in-plane spin lifetimes—can become giant (up to 100), depending on the TMDC, twist angle, transverse electric field, and the interlayer distance. The charge-to-spin conversion can be divided into three components which are due to spin-Hall and Rashba-Edelstein effects with nonequilibrium spin-density polarizations that are perpendicular and parallel to the applied charge current. All conversion efficiencies are highly tunable by the twist angle and the Fermi level.