Abstract Current and upcoming radio interferometric experiments are aiming to make a statistical characterization of the high-redshift 21 cm fluctuation signal spanning the hydrogen reionization and X-ray heating epochs of the universe. However, connecting 21 cm statistics to the underlying physical parameters is complicated by the theoretical challenge of modeling the relevant physics at computational speeds quick enough to enable exploration of the high-dimensional and weakly constrained parameter space. In this work, we use machine learning algorithms to build a fast emulator that can accurately mimic an expensive simulation of the 21 cm signal across a wide parameter space. We embed our emulator within a Markov Chain Monte Carlo framework in order to perform Bayesian parameter constraints over a large number of model parameters, including those that govern the Epoch of Reionization, the Epoch of X-ray Heating, and cosmology. As a worked example, we use our emulator to present an updated parameter constraint forecast for the Hydrogen Epoch of Reionization Array experiment, showing that its characterization of a fiducial 21 cm power spectrum will considerably narrow the allowed parameter space of reionization and heating parameters, and could help strengthen Planck's constraints on . We provide both our generalized emulator code and its implementation specifically for 21 cm parameter constraints as publicly available software.