This article addresses the inference of physics models from data, from the perspectives of inverse problems and model reduction. These fields develop formulations that integrate data into physics-based models while exploiting the fact that many mathematical models of natural and engineered systems exhibit an intrinsically low-dimensional solution manifold. In inverse problems, we seek to infer uncertain components of the inputs from observations of the outputs, while in model reduction we seek low-dimensional models that explicitly capture the salient features of the input–output map through approximation in a low-dimensional subspace. In both cases, the result is a predictive model that reflects data-driven learning yet deeply embeds the underlying physics, and thus can be used for design, control and decision-making, often with quantified uncertainties. We highlight recent developments in scalable and efficient algorithms for inverse problems and model reduction governed by large-scale models in the form of partial differential equations. Several illustrative applications to large-scale complex problems across different domains of science and engineering are provided.