A crystallographic study and theoretical analysis of the structural and La/Y site preferences in the La_5–xY_xSi₄ (0 ≤ x ≤ 5) series prepared by high-temperature methods is presented. At room temperature, La-rich La_5–xY_xSi₄ phases with x ≤ 3.0 exhibit the tetragonal Zr₅Si₄-type structure (space group P4₁2₁2, Z = 4, Pearson symbol tP36), which contains only Si–Si dimers. On the other hand, Y-rich phases with x = 4.0 and 4.5 adopt the orthorhombic Gd₅Si₄-type structure (space group Pnma, Z = 4, Pearson symbol oP36), also with Si–Si dimers, whereas Y₅Si₄ forms the monoclinic Gd₅Si₂Ge₂ structure (space group P2₁/c, Z = 4, Pearson symbol mP36), which exhibits 50% “broken” Si–Si dimers. Local and long-range structural relationships among the tetragonal, orthorhombic, and monoclinic structures are discussed. Refinements from single crystal X-ray diffraction studies of the three independent sites for La or Y atoms in the asymmetric unit reveal partial mixing of these elements, with clearly different preferences for these two elements. First-principles electronic structure calculations, used to investigate the La/Y site preferences and structural trends in the La_5–xY_xSi₄ series, indicate that long- and short-range structural features are controlled largely by atomic sizes. La 5d and Y 4d orbitals, however, generate distinct, yet subtle effects on the electronic density of states curves, and influence characteristics of Si–Si bonding in these phases.