Rare-earth elements (REEs: La–Lu, Y, and Sc) are integral to modern technology, but as technological development continues, world demand for these metals will increasingly outpace supply. Consequently, new and sustainable sources are needed, as well as more efficient methods of extraction and purification. Many waste streams—mining effluents, desalination brines, e-waste, and wastewater from semiconductor fabrication plants—contain high concentrations of REEs, which could be extracted. Metal-chelating polymers have great potential in REE extraction and separation applications due to their relatively low cost and high affinity for target elements, but tuning the interaction between the polymer and metal is often challenging. To investigate the interplay between polymer structure and metal chelation, we synthesized metal-chelating polymers with systematic variations in structure (chelating group, tacticity, hydrophobicity, etc.). We then used isothermal titration calorimetry to directly measure the binding affinity, enthalpy changes, and stoichiometry of the interactions between a series of REEs in solution and these metal-chelating polymers. These measurements enabled us to characterize the complete thermodynamic profile of these polymer-metal interactions. Further measurements of changes in heat capacity, along with computational data, reveal the key role of water during metal binding. Ultimately, this structure–function information will be used to design new materials that are more effective for REE extraction and separation.