Myosin molecular motors are involved in a range of diverse cellular processes, including muscle contraction, mechanosensation, intracellular transport, and membrane remodeling. All myosin isoforms share a conserved chemomechanical cycle that couples ATP hydrolysis to mechanical work on an actin filament. The kinetic and thermodynamic parameters that define this cycle, including duty ratio (the fraction of its cycle spent attached to actin) and ADP release rate (which controls actin detachment rate), can vary by orders of magnitude between isoforms, thus enabling this diversity of function. High resolution structures of the motor domains of many myosin isoforms have revealed surprising structural conservation between these biochemically diverse motors, raising the question as to how these motors are structurally tuned to such an array of molecular functions. We hypothesized that variability in the kinetic and thermodynamic parameters between isoforms results from alterations to the distribution of conformations a myosin adopts, and hence cannot be captured by any single structural model. To test this hypothesis, we performed over two milliseconds of explicit-solvent, all-atom molecular dynamics simulations for eight human myosin isoforms and constructed Markov state models (MSMs) of their free energy landscapes. These models capture significant conformational heterogeneity not observed in existing crystal models. We find that the relative populations of the two most probable conformational states predict biochemically measured duty ratios. Furthermore, the rates of transitioning between these populations predict ADP release rates measured in biochemical experiments. Finally, we investigate the role of allostery in modulating these crucial thermodynamic and kinetic parameters and suggest how perturbations at distant sites may be transmitted to and integrated at the active site. Taken together, our results shed light on myosin motors’ remarkable ability to provide vast physiologic diversity with the same structural fold.