- A man is sent to the flying city of Columbia to find a missing girl. However, upon arrival he discovers that the city, its people, and his objective are all not what they seem.
- The year is 1912, deep in debt, ex-Pinkerton agent Booker DeWitt is sent to the mysterious flying city of Columbia to find and retrieve a young woman imprisoned in a tower since birth - Elizabeth and to "Bring us the girl and wipe away the debt". However, almost as soon as Booker arrives, he finds that Columbia and its people are not quite what they seem, and all too soon science, religion, morality, family and life all clash and spiral down into utter chaos, with Booker and Elizabeth as unlikely partners in the midst of all the action.—Paddington
- July 6th, 1912, Booker DeWitt is a New York Pinkerton detective and Wounded Knee veteran given a curious task, to deliver a young girl to a client in New York, under the instruction of their representatives, the Lutece twins, Robert and Rosalind, they are extremely intelligent. His only lead is a picture of the girl, Elizabeth Comstock, whom has a missing right pinky finger that is covered with a thimble, bearing the message "Bring us the girl and wipe away the debt." The Luteces row him to a lone lighthouse off the coast of Maine.
Booker ascends the lighthouse alone to the top where he steps into a rocket chair that propels him through the clouds to a floating city called Columbia, a seemingly idyllic and technologically advanced civilization, on the day the city is celebrating the anniversary of Columbia's secession from the union of States. The leader is a religious figure, Father Zachary Hale Comstock. Booker spots a poster warning of a "false shepherd" that will take Columbia's "lamb," the shepherd is recognized by the letters 'AD' on the back of his right hand, as it happens, Booker has those exact letters carved on his right hand. Booker enters a fairground competition and discovers that race relations on Columbia are just bad on the surface, as he's won a prize to throw a ball at an interracial couple, here the player can choose to throw the ball at the couple or the host, Jeremiah Fink. Before throwing the ball at either, Booker is detained by police as they've spotted the telltale letters on his hand, Booker fights through the police and eventually makes it Monument Island where Elizabeth is held.
Naturally, she mistrusts a complete stranger offering to take her away, he offers to take her to her dream location of Paris, yet their escaped is hampered by the arrival of Songbird, a giant mechanical bird created with sole purpose of keeping Elizabeth in Columbia. Booker and Elizabeth narrowly escape dying during a plummet in the beaches of Columbia's Battleship Bay. They recover and spot a blimp floating overhead, The First Lady, their escape vessel. Getting to it however requires an item from the Hall of Heroes, dedicated to Columbia's accolades and Comstock's actions at Wounded Knee and the Boxer Rebellion. Booker was at Wounded Knee and remembers nobody called Comstock. On an elevator ride to the hall Elizabeth displays an ability to open tears to other dimensions.
Once aboard the First Lady Booker sets a course for New York, which Elizabeth notices as she spent most of her time in the tower reading many educational books, he explains his real reasons for freeing her and she knocks him out, when Booker regains consciousness, the airship is now occupied by the Vox Populi, a resistance group of Columbia's downtrodden minorities and their leader, Daisy Fitzroy, formerly a scullery maid to the Comstocks, wanted on suspicion of murdering First Lady Annabelle Comstock. Fitzroy will hand the airship over to Booker and Elizabeth in return for a supply of weapons from a Chinese gunsmith, Chen Lin. Booker is thrown off the ship and finds Elizabeth again, she mistrusts him, but since he's her only means of getting to Paris, she'll help him.
They head to Finkton, the Jeremiah Fink run industrial district, they head to Chen Lin's gun factory where his Chinese wife says the police took him to the Good Time Club for interrogation. He's found in the basement dead, a surprise appearance from the Lutece twins suggest Elizabeth use her powers to enter a dimension where Chen might be alive, they do so and find Chen at the factory in a strange state of alive and dead at once, due to one version of him being killed in an alternate timeline and that here he was spared because he was married to a Caucasian woman with ties to Finkton police. Chen's manufacturing equipment is being held at the police station, which means going through the Shantytown. Once at the station Elizabeth opens a new tear to a different Columbia, where Elizabeth was taken from Monument Island shortly after Booker's arrival and he joined the Vox Populi to further his task, but here died and is revered as a martyr for the current Vox revolution.
This knowledge causes Booker to suffer a spontaneous nosebleed, he and Elizabeth fight alongside the Vox to the First Lady, however Fitzroy only knows the Booker that died for the revolution and regards this new living version an imposter, the Vox turn on him. Booker and Elizabeth witness Daisy shoot Fink in cold blood and she takes his son hostage, Booker distracts her while Elizabeth sneaks behind Fitzroy and stabs her with a pair of scissors. They reclaim the First Lady and set off for Paris, only for Songbird to crash the ship into Emporia financial district.
An impromptu appearance from the Lutece twins provide information on Songbird's control mechanism, a specialized flute that plays a programmed tune, then they disappear. The leaderless Vox Populi are running rampant, killing civilians and destroying everything, many civilians are evacuating. They must make for Comstock House, yet cannot enter without specific authorization. Only the late Lady Comstock can provide it, they find her air-tight coffin at the cemetery, yet Comstock employs a siphon which drains some of Elizabeth's power to resurrect Lady Comstock in spectral form and attack them. They repel her, another appearance from the Lutece's explain that they must find tears to learn facts about the Comstocks.
In the tears it's revealed that due to the tears, Comstock was plagued with sterility and rapid aging and Elizabeth was not his child, but taken from another dimension, he had both his wife and the Luteces killed to hide this knowledge. With these details Elizabeth puts Lady Comstock to rest and they are gained access to Comstock House.
As they cross the bridge, Songbird attacks Booker again and almost kills him until Elizabeth intervenes, surrendering herself so Booker will be spared, Songbird takes off with Liz. Booker pursues them across the bridge and runs into a large tear that lands him in a snowy Columbia, Booker ventures on through the creepy surroundings only to find an elderly Elizabeth. They are overlooking New York City on New Year's Eve, 1983, when Columbia is attacking the surface. In this timeline, Elizabeth was indoctrinated into continuing Comstock's ideals and brought Booker to show him, furthermore, Songbird thwarted every attempt he made to rescue her, she provides him a card which shows how to control Songbird then sends him back to 1912 six months later. Booker enters the operating room where Elizabeth is being tortured and overloads the machines that grant her enough power to summon a tornado to destroy the room.
Their new goal is to kill Comstock and Songbird, which means boarding his personal airship, the Hand of the Prophet. Comstock is confronted in his cabin and he directs suspicion to Booker regarding Elizabeth's missing finger, Booker manhandles Comstock and drowns him in a baptismal font, this causes Booker to have another nosebleed. They continue to the deck, Elizabeth obtains a whistle that enables control over Songbird, it is used to wipe out the last of the attacking Vox Populi and destroy Monument Island statue which contains a siphon that restrains Elizabeth's full power. The destruction of the siphon damages the whistle and Songbird turns toward them, Elizabeth opens a large tear into the underwater city of Rapture. Songbird is trapped outside in the ocean and is crushed under the pressure.
They ride a bathysphere to the surface lighthouse, through the door they enter a sea of lighthouses where alternate versions of Booker and Elizabeth are concluding their adventures. Elizabeth's now unrestrained power has granted her omniscience and a view into Booker's past. During the battle of Wounded Knee Booker committed many atrocities for which he felt guilt for, he attended a baptism, but he back out at the last minute as he felt it wasn't enough to erase the damages done. Later he would marry, his wife would give birth to a daughter named Anna in 1893, but the woman died during birth. Booker fell into a state of depression and squandering, putting himself in debt, until the Luteces appeared with the offer to "bring the girl", Booker complied but changed his mind and ran to a street where Comstock was stepping through a tear to his reality, Booker tried to grab Anna back but lost her, as she went through the tear closed on her right pinky finger, severing it.
Elizabeth was Anna, a part of her in one world gave her the ability to create tears. After the Luteces were killed, versions of them were spread across realities, which allowed them to find Booker in 1912, in a worse state after losing Anna, having carved the letters 'AD' on his hand, they offered him a deal, their real goal was to return Anna to her real father, knowing she would one day destroy the world. They bought Booker to Maine through a tear, however entering the tear caused paradoxes that erased Booker's memory, making him believe it was just a typical assignment.
Booker apologizes to Elizabeth for giving her away and that they can move on, but there's more to it than that. Comstock will always exist in other universes, they must remove the source of him. Booker is taken back to the where he was almost baptized surrounded by many alternate Elizabeths, in one timeline he refused, but in another he took the cleansing and was reborn, as Zachary Hale Comstock. Booker lets the Elizabeths drown him, erasing all versions of Comstock and as he drowns the Elizabeths disappear one by one.
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