Highly active and durable electrocatalysts for oxygen evolution reaction (OER) play significant roles in renewable energy technologies such as water electrolysis and metal-air battery. Here we report a simple and effective strategy to improve the OER electrocatalytic performances of a high-entropy perovskite La(CrMnFeCo2Ni)O3 (LaB2Co) by A-site acceptor doping. A series of La1–xCaxB2Co (0 ≤ x ≤ 0.4) was prepared, and their electrocatalytic activity and stability towards OER in 1 M KOH solution were investigated. Results show that the OER overpotential (at 10 mA cm–2) decreases with increasing doping level from 386 mV for x = 0 to 340 mV for x = 0.4. The optimum composition, La0.6Ca0.4B2Co, also exhibits excellent long-term stability that the potential at 10 mA cm–2 varies less than 20 mV in 200 h. The prominent OER activity of La0.6Ca0.4B2Co is attributed to the presence of high-level oxygen vacancies, as well as rich oxidation states of the active elements on the surface of the perovskite. The superior OER durability is beneficial from the high configurational entropy, which provides sufficient active sites during durability tests. Findings from this work prove that acceptor doping is an effective strategy to improve the activity and durability of perovskite-type high-entropy oxides as OER electrocatalysts.