|For Thanos' cosmic hideout, see Sanctuary.|
It was likely named after Thanos' previous base of operations, Sanctuary.
Intercepting the Asgardians
With the help of the Black Order and the Power Stone, Thanos was able to slaughter half of the Asgardians on the Statesman and add the Space Stone into the Infinity Gauntlet. Despite Heimdall and Loki being killed in the ordeal, Thor, Hulk, Valkyrie and a handful of Asgardians were able to escape.
After Thanos obtained the Reality Stone and kidnapped Gamora on Knowhere, he used the Space Stone to teleport both of them to the Sanctuary II. While in the ship's throne room, Thanos revealed to Gamora that he knew all along that she learned the location of the Soul Stone years ago. Having captured Nebula when she snuck aboard the Sanctuary II some time ago to kill him, Thanos used the Infinity Gauntlet to torture her until Gamora confessed that the Soul Stone was on Vormir to save her adoptive sister.
After Thanos and Gamora went to Vormir to obtain the Soul Stone, a Chitauri reassembled Nebula's cybernetics and was killed when she faked a malfunction and took it by surprise. After escaping from her captivity, Nebula contacted Mantis and requested that she and the rest of the Guardians of the Galaxy meet her on Titan, knowing that the members of Thanos' Black Order would meet him there once they found the Time Stone and Mind Stone. Nebula then took a Necrocraft and left the Sanctuary II to meet her allies on Titan.
In 2014, Thanos used the Sanctuary II as an orbital base to attack an unnamed planet. Upon learning that Ronan the Accuser had discovered the location of the Power Stone on Morag, Thanos returned to the ship. Before he could dispatch Gamora and Nebula to aid Ronan, Nebula's implants synchronized with those of her 2023 self, who had traveled to the past with War Machine to retrieve the Power Stone. While War Machine was able to return to 2023 with the Power Stone, 2023 Nebula was anchored in the past due to her link with 2014 Nebula. Thanos was also able to track her location due to this link, and he brought the Sanctuary II to Morag, where he beamed her aboard the ship.
2014 Nebula took Pym Particles from her captive 2023 counterpart and presented them to Thanos. 2014 Nebula then traveled to 2023 in her future self's place. Once there, she used the Avengers' time machine the Sanctuary II through the Quantum Realm to 2023. Emerging from the time machine, the rapidly growing warship punched through the roof of the New Avengers Facility, destroying the time machine in the process. The Avengers initially did not notice, as they were working on the Reversal of the Decimation. Very shortly after the Decimation was undone, the Sanctuary II bombarded the New Avengers Facility with missiles, destroying it completely. Thanos then beamed down from the hovering ship and commanded 2014 Nebula to find the Infinity Stones, and also deployed a group of Outriders from the ship for the same purpose.
After fighting and defeating Captain America, Iron Man, and Thor, Thanos summoned the Black Order from the ship alongside a vast army, consisting of many thousands of Chitauri, Outriders, Necrocraft, Leviathans , and Chitauri Giant Dogs. When Thanos began losing his battle against Scarlet Witch, he ordered Corvus Glaive to have the Sanctuary II direct its energy cannons at the battlefield. This bombardment stopped Scarlet Witch from killing Thanos, and it also destroyed a nearby dam, forcing Doctor Strange to leave the battle in order to prevent a flood. The Sanctuary II then detected the approach of Captain Marvel from space and directed its fire at her as she descended, but the ship's cannons had no effect on her. Captain Marvel crashed through the ship's bow and wings, virtually destroying it and sending it crashing down to Earth.
What remained of the Sanctuary II was reduced to dust when Iron Man used the Infinity Stones to destroy Thanos and his army.