In 2045, Luna was colonized and the New Horizons Lunar Colony was created. In 2514, the Unitologist extremist group, the Circle led by Jacob Danik) attacked Luna's colony. They succeeded in their endeavor to "free" the planet's Marker from the Earth Government-facilitated shroud and to kill Isaac Clarke for his actions in Titan Station. Their actions resulted in a Necromorph outbreak which presumably wiped out the New Horizons Lunar Colony.
After the outbreak, Isaac Clarke and Sgt. John Carver returned to Earth and Luna in the CMS Terra Nova recovered from above Tau Volantis. They attempted to contact anyone on the radio channels on Earth and Luna. However, all of what they received was people being slaughtered by the Necromorphs. They later found out that the Brethren Moons arrived at Earth and are attempting to exterminate the human race. The Terra Nova then started crashing into the Moon.