One of the main challenges in drug discovery is predicting protein-ligand binding affinity. Recently, machine learning approaches have made substantial progress on this task. However, current methods of model evaluation are overly optimistic in measuring generalization to new targets, and there does not exist a standard dataset of sufficient size to compare performance between models. We present a new dataset for structure-based machine learning, the CrossDocked2020 set, with 22.5 million poses of ligands docked into multiple similar binding pockets across the Protein Data Bank and perform a comprehensive evaluation of grid-based convolutional neural network models on this dataset. We also demonstrate how the partitioning of the training data and test data can impact the results of models trained with the PDBbind dataset, how performance improves by adding more, lower-quality training data, and how training with docked poses imparts pose sensitivity to the predicted affinity of a complex. Our best performing model, an ensemble of 5 densely connected convolutional newtworks, achieves a root mean squared error of 1.42 and Pearson R of 0.612 on the affinity prediction task, an AUC of 0.956 at binding pose classification, and a 68.4% accuracy at pose selection on the CrossDocked2020 set. By providing data splits for clustered cross-validation and the raw data for the CrossDocked2020 set, we establish the first standardized dataset for training machine learning models to recognize ligands in non-cognate target structures while also greatly expanding the number of poses available for training. In order to facilitate community adoption of this dataset for benchmarking protein-ligand binding affinity prediction, we provide our models, weights, and the CrossDocked2020 set at https://github.com/gnina/models.