A new way to use wide-angle x-ray solution scattering to study protein-ligand binding is presented. First, scattering patterns are measured at different protein and ligand concentrations. Multivariate curve resolution based on singular value decomposition and global analysis is applied to estimate the binding affinities and reference patterns (i.e., the scattering patterns of individual components). As validated by simulation, Bayesian confidence intervals provide accurate uncertainty estimates for the binding free energies and reference patterns. Experimental results from several protein-ligand systems demonstrate the feasibility of the approach, which promises to expand the role of wide-angle x-ray scattering as a quantitative biophysical tool.