A mixed crystal strategy is reported as an effective approach to improving the performances of inorganic scintillators for radiation detection applications. The aim of this work is to optimize ternary iodide KCaI3:Eu2+ single crystals via partial Sr2+ substitution, and to provide physical insights and a strategy of designing promising halide scintillators. The ∅22 mm × 50 mm long K(Ca,Sr)I3:Eu2+ single crystals are grown by the Bridgman method. Crystal structure refinements verify the phase purity and the orthorhombic crystal system with a space group of Cmcm (No. 63) in the solid solutions. An energy resolution of 2.5 ± 0.1% at 662 keV and a light yield of 74 000 ± 4000 photons per MeV can be achieved for a 4 mm cube KCa0.835Sr0.165I3:Eu2+. It is for the first time that a halide solid solution is synthesized with a competitive scintillating performance as current state-of-the-art scintillators, such as SrI2:Eu2+ and LaBr3:Ce3+. A combination of first-principles calculations and optical characterization experiments is employed to construct the host material band edges and the relative positions of 5d and 4f energy levels of the Eu2+ activation center. The origins of the improvement of light yield and scintillation response nonproportionality are proposed from experimental and theoretical insights.