The oxidative coupling of methane (OCM) to C2 hydrocarbons is one of the most attractive catalytic processes towards the effective utilization of methane. Despite a great deal of effort in past research, the primary activation factor for OCM has still been unclear because of the chemical and structural complexities of known catalysts such as Mn−Na2WO4/SiO2. Here, we report a high catalytic activity of a crystalline oxide Li2CaSiO4 for OCM. The C2 selectivity and CH4 conversion reach 77.5 % and 28.3 %, respectively, at 750 °C, which are comparable to or even higher than those with Mn−Na2WO4/SiO2. The simplicity of active sites in our single‐phase Li2CaSiO4 catalyst facilitates a deeper understanding of the reaction mechanism, which leads to a crystallographic design concept for highly active OCM catalysts containing multiple cations.