We discuss a general framework to address spin decoherence resulting from fluctuations in a spin Hamiltonian. We performed a systematic study on spin decoherence in the compound K-6[V15As6O42(D2O)]center dot 8D(2)O, using high-field electron spin resonance. By analyzing the anisotropy of resonance linewidths as a function of orientation, temperature, and field, we find that the spin-orbit term is a major decoherence source. The demonstrated mechanism can alter the lifetime of any spin qubit and we discuss how to mitigate it by sample design and field orientation.