The Abadon Mutie Uprising was a major conflict between humans and Mutants.
As it isn't show in game, there aren't much details about the Rising. However, it is known than it happened in some date between 2135 and 2165. After the Authority Wars, the Ark Survivors built an unknown number of Ark Settlements. However, in the Uprising all were overrun by the mutants, until only Vineland survived. In 2165, the mutants' nests in the Wastelands still posed a serious threat to other human settlements.