External control on chemical reactivity requires understanding the fundamental forces governing reactions at molecular length scales, where interactions with the environment can affect reaction outcomes. In single crystals, reactivity is governed by lattice-constrained molecular packing and unique electrostatic potentials leveraged by specific system-bath interactions that are absent in the solution phase. However, sample depletion and product accumulation have made studies of ultrafast photochemical reactions in crystals challenging. Here, we present the first report of ultrafast spin-vibronic-mediated intersystem crossing (ISC) leading to intramolecular charge transfer in single crystals of binuclear platinum complexes. Ultrafast spectroscopic measurements with advanced time-frequency analysis reveal a 10-fold increase in ISC rate compared to solution phase, arising from lattice effects in tuning the energetics for the singlet–triplet manifolds. Additionally, comparative studies of structurally analogous platinum complexes demonstrate the critical role of bath-controlled tuning of an intermediate state in facilitating efficient ISC. These observations are further supported by quantum-dynamical calculations that predict a systematic variation of ISC rates with the singlet–triplet energy gap, elucidating a general framework for structure-guided control of ISC dynamics through system-bath interactions.