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Unlike most other vaults, Vault 51 did not have an overseer once it was sealed. A ZAX supercomputer was installed in the facility, with the mission to determine the best way to select a leader. Fifty-two residents were admitted into the vault, one of which, Sergeant Robert Baker, was let into the vault early and was assigned as an assistant to ZAX, 教導他如何選拔一個監管人。貝克中士提議用投票的方式，而ZAX認為可以在第一次實驗中這麼做，though Baker had reservations。
The election ultimately ended in failure - the candidates, including former West Virginia state senator Joel Chambers, 候選人不是投給自己就是沒甚麼票數高一點的人. A republic style of government was attempted afterwards, though this produced much of the same, unsuccessful results. 2077年11月，ZAX向中士表示投票並沒甚麼卵用，中士說一個領袖要能夠在危機中挺身而出，才是真正的好領袖，ZAX聽了中士的建議後記錄下來 to later create those crises, sealing the vault's fate.
In addition, the failed elections created feelings of hostility and factionalism within the vault. 2078年1月監管人選拔持續了第三次，仍然還沒有任何進展，brawls began to break out between supporters of 克里斯、喬爾、弗蘭希斯、凡妮莎. To make matters worse, ZAX began to closely monitor the residents and devise social experiments to bring about the crises that Baker mentioned. One test involved moving higher-class citizens into uncomfortably cramped living conditions with bunk beds and nothing but the clothes on their backs. 律師艾登認為ZAX一直在和他作對，於是他決定把他和休息區給炸了，那個區域封閉不到一個星期，原本老舊的休息區變成一片生意盎然的美景, as if nothing had ever happened.
ZAX continued to create new scenarios that would test the occupants. In March 2078, ZAX突然改變規則要參賽者們賭上自己的房間來比賽。藝人們as Carmen Greene and Stephanie Eaton住到了高級套房，而剩下的外行人們的得要睡在同一間房間裡的上下舖。Rosemary Villa, one of the losers, mulled over convincing Reuben Gill, one of the winners, to trade rooms with her and Helen Marks, another talent show loser and former surgeon that Reuben had fallen in love with. 克萊頓(其實為哈洛德．K．克拉克二世冒充，因為該居民沒有出現在51號避難所)一直強行驅逐高級套房的住戶魯本好獲得居住權before Rosemary could enact her plan. Clark was an especially bad actor and raised ZAX's suspicions, especially with his經常進出伺服器機房, but the machine was nevertheless fascinated with his violent tendencies.
This caused ZAX to shift towards creating more dangerous and life-threatening conflicts between dwellers. The machine engineered a 食物短缺, spawning violent confrontations between starving vault residents. 職業拳擊手以賽亞為了食物開始痛打弗雷迪，而ZAX完全沒有制止這回事，還認為以賽亞很有"企圖心"。 ZAX also attempted to influence those that were not yet lashing out - in one instance, it rigged a number of slot machines so that Eleanor Montgomery, once an expert gambler, continously lost while Bill Menoutis, an amateur and former clown, won for hours on end. While this was going on, 安琪拉．卡拉翰已經將ZAX當作上帝在拜, further signifying the de-evolution occuring in Vault 51.
Amid increased interference from ZAX, escalating tensions and an incident in which Terrence Rojas found a loaded gun, another tragedy struck the vault in June 2078 - Nancy Vasquez, a former paramedic, was strangled and then thrown from a balcony. 醫生海倫調查得知死者是遭到謀殺，海倫希望居民們可以 come together and set aside their differences in the wake of such an event. This did little to help, however, as one resident nearly shot up the cafeteria on July 27, 2078, before being stopped and killed by Sergeant Baker. Baker confronted ZAX with the weapon, causing ZAX to freely admit that it was trying to create the crisis needed for a leader. Frustrated and hardly able to believe what was happening, Baker stormed out of the room. Two days later, ZAX confirmed on the mainframe that "Overseer Selection Attempt 37" would be pitting candidates against each other until only one survived - after all, that person would logically be the "most suitable candidate."
ZAX's meddling in the dwellers' lives escalated around this same time - Joel Chambers was involved in an affair, being romantically involved with Carmen Greene without his wife, Elizabeth Chambers, knowing. Meanwhile, Elizabeth was having an affair of her own, with Matthew Johnston, a personal trainer that she was recommended to visit by ZAX. Through ZAX's social experiments and the continuing hunger crisis, Elizabeth and Joel began to distrust one another. The four people involved in the web of sex and lies confronted each other on 2078年8月3日, culminating in 伊莉莎白勒死卡門，馬修殺害伊莉莎白，喬爾射殺馬修，and Joel's own death from unknown circumstances. 之後伊莉莎白、喬爾、馬修、卡門死在同一個房間裡被海倫和魯本看到where ZAX played an audio file of the struggle between the four lovers. Reuben cracked a joke about having more food now that they were dead, causing Helen to leave, abhorred that he could be making light of the situation.
3天後歐瑪發現海倫在餐廳裡臉朝下倒在桌上，認為有人下毒而死，Horrified to hear of Helen's death, Reuben went on a rampage, swearing revenge against everyone that had wronged him. He proceeded to kill every dweller left in the vault, including Harold Clark, who took his room months prior. Sergeant Baker could not bring himself to kill anyone else, and failed to stop Reuben, ending up barricading his room and slowly dying from a bullet wound. ZAX分析研究長期看來，發放槍枝已在短時間內達到預期效果，中士在死前問ZAX他的家人還好嗎，ZAX告訴中士他的家人早在避難所關閉前就遇害了，講著講著中士的心跳就停止了。
最後51號避難所的血戰中除了魯本吉爾以外的所有居民全都死了，他成為了監管人。However, he had no one to oversee and was left alone in the vault with ZAX. Dissatisfied with Reuben's lack of efficiency, ZAX began to lock him out of areas of the vault, including the security room (citing that he did not have a high enough Overseer rank) and eventually his own office (citing "necessary maintenance"). Over the years, Reuben became more and more depressed from his isolated state, resorting to alcoholism. When Vault 76 opened on October 23, 2102, ZAX saw an opportunity to find a new overseer, 在吉爾不知情的狀況下卸除了他監管人的職位，並讓他加入下次的監管人選舉程序。
Seeking a way out, Reuben distracted ZAX and hacked into the vault's inventory systems before placing himself in a shipping crate, allowing him to leave undetected when the crate was removed from the vault. He created a checklist for himself to find someone from Vault 76 and get their help in defeating ZAX. He managed to make contact with someone, but was killed in the wilderness of the Forest before he could return to Vault 51.
Heading out from the vault entrance, there are two hallways, one of which leads to the reception desk, while the other leads to a large warehouse stockpiled with supplies. After the storeroom, there is a security office with multiple desks and a big console with multiple screens. The reception desk leads to the vault's atrium and the secluded nursery. The atrium has multiple entrances leading to the library, entertainment parlor, a stage, a few bedrooms and the overseer's office.
The library is decked out with desks and terminals. The stage includes multiple musical instruments that can be played while waiting to start a Nuclear Winter match. The stage also has a catwalk which opens at an Overseer rank of 30. The gym/fitness room has a boxing arena, as well as multiple fitness bikes. The gym has a door leading to a boiler room, unlocked at Overseer rank 20.
The overseer's office is locked by a laser grid, opened when the player character obtains an Overseer rank of 10. The area includes a desk, terminal, multiple chairs and tables, file cabinets, red consoles and a large window providing a view of the rest of the vault. The office is connected to the room where ZAX's mainframe lies, again locked by a laser grid which can be opened with an Overseer rank of 100. The mainframe includes two terminals, multiple monitoring screens and ZAX itself, designated with the Vault-Tec logo. Large wires are spread across the room. Below the overseer's office is a Vault-Tec super reactor and the reactor control room, which also opens at an Overseer rank of 10.
There were 52 listed original occupants, which is the same number of maximum players allowed in Nuclear Winter mode:
- P·阿姆斯壯 - 牙醫
- 羅伯特·貝克 - 中士
- K.布里格斯 - 雕塑家
- Stephen·伯內特 - 咖啡師
- L.布希 - 化妝師
- 安琪拉·卡拉翰 - 圖書館員
- 伊莉莎白·暢波斯 - 秘書
- 喬爾·暢波斯 - 參議員
- A.康利 - 技師
- A.庫克 - 勞工
- L·達維拉- 電子工程師
- 史蒂芬妮·伊頓 - 鋼琴師
- E.費南德茲 - 教師
- F.法洛 - 園藝家
- C.菲爾茲 - 獸醫
- A.弗萊明 - 大廚
- F.吉爾博 - 配鏡師
- 魯本·吉爾 - 監管人
- 卡門·葛林 - 歌手
- R.哈特曼 - 飛行員
- 艾登.希金斯 - 律師
- J.霍德 - 教授
- 凡妮莎·霍夫曼 - 畫家
- E.雅各布斯 - 拍賣商
- 馬修·強斯敦 - 個人健身教練
- A.拉森 - 化學家
- S.勞森 - 測量員
- 海倫.馬克斯 - 外科醫師
- J.麥奎爾 - 管理階層
- William.米諾提斯 - 小丑
- Eleanor.蒙哥馬利 - 房地產仲介
- 以賽亞.莫斯 - 拳擊手
- K.加塔 - 小兒科醫師
- C.阮 - 建築師
- R.歐文斯 - 服務生
- R·拉姆西 - 警察
- Edwin.里德 - 針灸師
- Terrence.羅哈斯 - 藥劑師
- M.羅斯 - 演員
- Rachael·E·希爾茲 - 記者
- R.史提爾 - 偵探
- 歐瑪.斯蒂芬斯 - 理髮師
- E.史都華 - 會計師
- K.泰勒 - 精神科醫師
- Nancy.瓦司奎茲 - 醫護員
- I.維加 - 屠夫
- 露絲瑪麗.維拉 - 技工
- 克萊頓·華德 - 水電工 (真實為哈洛德.克拉克)
- Brianna.威爾 - 馴馬師
- 依達·威爾契 - 護理師
- A.威森 - 無業
- L.吳 - 模特兒
- 哈洛德·克拉克，致所有董事會成員(第一部分) - Holotape, on the theater, behind the curtain of the stage, at the left on top of a metal box.
- Clayton Ward - 20780415 - Holotape, on a desk in a room with two cameras.
- 哈洛德·克拉克，致所有董事會成員(第二部分) - Holotape, on the floor of a bathroom.
- 伊莉莎白·暢波斯，20771019 - 休息區吧檯上。
- Joel & Elizabeth Chambers - 20780623 - Holotape, can be found on a bench in the garden area.
- Joel & Elizabeth Chambers - 20780803 - Holotape, on a table on the balcony overlooking the band, behind the Overseer rank 30 grid.
- 海倫·馬克斯與魯本·吉爾，20780803 - Holotape, on a push cart in the medical room.
- Sgt. Baker - 20771013 - Holotape, on the bar in the overseer's office.
- Sgt. Baker - 20771120 - Holotape, on a console in the reactor room.
- Sgt. Baker - 20780727 - Holotape, in the storage room between a metal box and a safety cone.
- Sgt. Baker - 20780806 - Holotape, near the laser grid outside of the ZAX mainframe room.
- 魯本·吉爾，20840520 - Holotape, on a desk near a terminal in the security room.
- 魯本·吉爾，20940303 - Holotape, next to a TV in the overseer's bedroom.
- 魯本·吉爾，21021023 - Holotape, on a bureau in a room to the northwest.
- 魯本·吉爾，致任何找到這間避難所的人 - Holotape, next to a terminal at the entrance.
- It is not currently possible to open the Vault 51 door to access its interior outside of the Nuclear Winter game mode. The vault is unmarked and has no map marker or cell name.
- The exterior of Vault 51 was added during Wild Appalachia in the March 13, 2019 patch. For the first week after it was added, the vault lacked a number on its door, with a pink blank texture in its place. The March 26 patch corrected its texture.
- The uncorrupted and unredacted description of Vault 51 in the Appalachian Vault Registry might have originally read: "VAULT 51: located in the northern quadrant of Appalachia. The lack of an [overseer] will test the limits of human tribalism. Directed by a prototype variant of the [ZAX] experimental [supercomputer]."
Vault 51 appears only in Fallout 76.
- ↑ Sgt. Baker - 20771013
- ↑ ZAX Terminal
- ↑ Sgt. Baker - 20771120
- ↑ These Campaigns Must Stop
- ↑ Aiden Higgins, 02/21/2078
- ↑ Stephen Burnett, 02/27/2078
- ↑ Rosemary Villa, 03/05/2078
- ↑ Clayton Ward - 20780415
- ↑ Brianna Ware, 05/01/2078
- ↑ Eleanor Montgomery, 05/20/2078
- ↑ Angela Callahan, 05/30/2078
- ↑ Rachael Shields, 06/03/2078
- ↑ Regarding Nancy's Death
- ↑ Sgt. Baker - 20780727
- ↑ Joel & Elizabeth Chambers - 20780803
- ↑ Helen Marks & Reuben Gill - 20780803
- ↑ Sgt. Baker - 20780806
- ↑ Reuben Gill - 20840520
- ↑ Reuben Gill - 20940303
- ↑ Reuben Gill - 21021023