The article briefly discusses the key achievements of the enterprise over 75 years from the formation of OKB-1 headed by S.P. Korolev for producing intercontinental range missiles to the current status of RSC Energia being the country’s and world leader in manned space flight. The developed intercontinental missiles R-7 and a closed-loop oxygen-hydrocarbon liquid-propellant rocket engine provided the basis for developing integrated launch vehicles which were used to launch the world’s first Earth satellite, the first cosmonaut on the Earth, automatic interplanetary stations to the Moon, Venus, Mars. The diversification of the enterprise impeded S.P. Korolev to concentrate on manned space flights, and he initiated the transfer of development and manufacture of combat missiles to V.P. Makeev DB, integrated launch vehicles to TsSKB Progress, communication and other satellites to M.F. Reshetnev ISS, lunar and interplanetary stations to S.A. Lavochkin NPO. In the 1980s under the guidance of V.P. Glushko the Energia super-heavy launch vehicle and Energia–Buran system in unmanned configuration were developed and successfully launched on the first try. The Salyut manned single-module orbital stations, Mir multifunctional multi-module space laboratory and successfully operating upgraded manned transportation (Soyuz) and logistics (Progress) spacecraft were developed. In the hard times of 1990s, RSC Energia under the guidance of Yu.P. Semenov saved the national cosmonautics through commercial research performed on the Mir station. At present, RSC Energia together with Khrunichev Space Center is completing the stage of ground tests of a multipurpose laboratory module and is manufacturing modules for a promising near-Earth manned station.