A framework is developed for optimizing magnetization transfer experiments for measuring first‐order rate constants of a two‐component exchange network. In the analysis the spin‐lattice relaxation time of the non‐saturated resonance is assumed to be known. However, we demonstrate that our work can also be applied to cases in which the spin‐lattice relaxation time falls within a physiologically reasonable range for this parameter. We provide an algorithm for the parameters permitting the experimenter to optimize the selection of measurement times in order to control the error in a worst‐case scenario. In addition, we compare the performance of the time‐dependent saturation experiment with an inversion experiment in this framework, finding that the former always leads to a more effective design.