Amine-based extraction processes are broadly exploited for the selective extraction of uranium from sulfuric leaching liquors. The molecular forces (that is, the enthalpy associated with the multi-scale structuration of tertiary amines) are balanced by entropic effects that have not yet been identified. This first part in a series of reports describes the effects of the alkyl chain configuration on the phase stability and aggregation properties of tertiary amines. It is demonstrated that tertiary amines with longer or slightly branched alkyl chains provide better phase stability and enable constant extraction of uranium. In comparison, more branching of the alkyl chains hinders the formation of a highly curved interfacial layer, thus preventing efficient extraction. Combined small-angle scattering determination of the nanostructures in the organic phase and oil–water surface tension measurements revealed that the alkyl chains effects on the efficiency of the extraction process and phase stability are associated with reverse aggregates with smaller polar core volumes and less co-extracted water, suggesting that packing of the alkyl chains has a direct impact on the extraction efficiency of the solvent extraction system.