The process of amino acid replacement in proteins is context-dependent, with substitution rates influenced by local structure, functional role, and amino acids at other locations. Predicting how these differences affect replacement processes is difficult. To make such inference easier, it is often assumed that the acceptabilities of different amino acids at a position are constant. However, evolutionary interactions among residue positions will tend to invalidate this assumption. Here, we use simulations of purple acid phosphatase evolution to show that amino acid propensities at a position undergo predictable change after an amino acid replacement at that position. After a replacement, the new amino acid and similar amino acids tend to become gradually more acceptable over time at that position. In other words, proteins tend to equilibrate to the presence of an amino acid at a position through replacements at other positions. Such a shift is reminiscent of the spectroscopy effect known as the Stokes shift, where molecules receiving a quantum of energy and moving to a higher electronic state will adjust to the new state and emit a smaller quantum of energy whenever they shift back down to the original ground state. Predictions of changes in stability in real proteins show that mutation reversals become less favorable over time, and thus, broadly support our results. The observation of an evolutionary Stokes shift has profound implications for the study of protein evolution and the modeling of evolutionary processes.