Launched on 2 June 2003 and arriving at Mars on 25 December 2003 after a 7-month interplanetary cruise, Mars Express was the European Space Agency’s first mission to arrive at another planet. After more than 20 years in orbit, the spacecraft and science payload remain in good health and the mission has become the second oldest operational planetary orbiter after Mars Odyssey.This contribution summarizes the Mars Express mission operations, science planning and data archiving systems, processes, and teams that are necessary to run the mission, plan the scientific observations, and execute all necessary commands. It also describes the data download, the ground processing and distribution to the scientific community for the study and analysis of Mars sub-surface, surface, atmosphere, magnetosphere, and moons.This manuscript also describes the main challenges throughout the history of the mission, including several potentially mission-ending anomalies. We summarize the evolution of the ground segment to provide new capabilities not envisaged before launch, whilst simultaneously maintaining or even increasing the quality and quantity of scientific data generated.