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Abstract Electron ptychography provides new opportunities to resolve atomic structures with deep sub-angstrom spatial resolution and to study electron-beam sensitive materials with high dose efficiency. In practice, obtaining accurate ptychography images requires simultaneously optimizing multiple parameters that are often selected based on trial-and-error, resulting in low-throughput experiments and preventing wider adoption. Here, we develop an automatic parameter selection framework to circumvent this problem using Bayesian optimization with Gaussian processes. With minimal prior knowledge, the workflow efficiently produces ptychographic reconstructions that are superior to those processed by experienced experts. The method also facilitates better experimental designs by exploring optimized experimental parameters from simulated data.