Large-scale battery systems are essential for efficiently utilizing renewable energy power sources from solar and wind, which can generate electricity only intermittently. The use of lithium-ion batteries to store the generated energy is one solution. A long cycle life is critical for lithium-ion battery when used in these applications; this is different from portable devices which require 1,000 cycles at most. Here we demonstrate a novel co-substituted lithium iron phosphate cathode with estimated 70%-capacity retention of 25,000 cycles. This is found by exploring a wide chemical compositional space using density functional theory calculations. Relative volume change of a compound between fully lithiated and delithiated conditions is used as the descriptor for the cycle life. On the basis of the results of the screening, synthesis of selected materials is targeted. Single-phase samples with the required chemical composition are successfully made by an epoxide-mediated sol-gel method. The optimized materials show excellent cycle-life performance as lithium-ion battery cathodes.