Controlling the distribution of chemical constituents within complex, structurally heterogeneous systems represents one of the fundamental challenges of alloy design. We demonstrate how the combination of recent developments in sophisticated experimental high resolution characterization techniques and ab initio theoretical methods provide the basis for a detailed level of understanding of the microscopic factors governing compositional distributions in metallic alloys. In a study of the partitioning of Mg in two-phase ternary Al–Sc–Mg alloys by atom-probe tomography, we identify a large Mg concentration enhancement at the coherent α-Al/Al 3Sc heterophase interface with a relative Gibbsian interfacial excess of Mg with respect to Al and Sc, Γ Mg rel , equal to 1.9 ± 0.5 atom nm −2. The corresponding calculated value of Γ Mg rel is ∼1.2 atom nm −2. Theoretical ab initio investigations establish an equilibrium driving force for Mg interfacial segregation that is primarily chemical in nature and reflects the strength of the Mg–Sc interactions in an Al-rich alloy.