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Escape the Nautiloid
The first major Quest of Baldur's Gate 3, Escape the Nautiloid, takes place immediately after the opening cinematic. The player character, now infected with a mind flayer tadpole, is aboard the Nautiloid ship when it is attacked by githyanki warriors. While trying to escape, the Mind Flayer controlling the ship warps the Nautiloid through different planes of existence before ending in Avernus, the first of the Nine Hells. The objective of the Prologue is to find a way out of the Nautiloid, ideally by not dropping down into Hell.
Objectives
Walkthrough
Nursery Room
The game begins in the Nursery, where the player character breaks free from a Mind Flayer Pod. Empty mind flayer pods are scattered throughout the room, indicating that there might be other survivors.
A mind flayer "nursery" i.e. a pool filled with larvae can be found in the center of the room. Passing a 
DC 10 Investigation check reveals that the casing is fragile. If touching the pool, it explodes and causes damage. Health can be restored at the Restoration device on the western side of the room at X: 33 Y: -428.
South of the nursery, the body of a mind flayer can be looted for a random gem at X: 43 Y: -429.
Farther south of the mind flayer, a raised path leads to a 
Cartilaginous Chest containing random loot at X: -43 Y: -440.
Toward the eastern side of the room, another raised path leads to an elevated area, which curves along the northwest side of the room. An 
Onyx and 
Rune Slate can be found on a table at X: 50 Y: -408. Interacting with the slate confers visions of the Nautiloid traveling through the Planes.
Past this table, another Cartilaginous Chest with loot can be found at X: 36 Y: -409.
To advance to the next room, enter through the door next to the restoration device on the western side of the room at X: 24 Y: -423.
Surgery Room
Immediately upon entering the surgery room, a table can be found containing an Illithid Record and Goblin corpse. Interacting with the record imparts images of Goblin history and culture. The corpse can be looted for a small amount of Gold.
North-west of the table, three additional rune slates can be found, which provide more images of the Nautiloid and an anomalous feeling.
On the far north side of the room, an Eldritch Tablet reveals images of Humanoid history.
In the middle of the room, a small elevator leads to an upper level. Interacting with the Neural Apparatus will raise the platform. On the upper level, a high elf named Myrnath can be found with a removed scalp, their exposed brain telepathically pleading for help.
The Intellect Devourer
When interacting with Myrnath, if succeeding a DC 10 Arcana check, it is revealed that the exposed brain is an intellect devourer. It is possible to free, abandon, or destroy the brain. If the player character decides to free the creature it can be asked about its name, which is Us. The creature will task the player character to reach the Helm and take control of the Nautiloid. It is also possible now to obtain Us as an attached follower.
Before freeing Us, if the passing a DC 10 Investigation check, a cerebral extraction can be done by passing a DC 10 Medicine check with 
Advantage. Otherwise, a DC 10 Strength, or Dexterity check must be passed.
After freeing Us, the player character can mutilate the creature by passing a DC 15 Dexterity check. On failure, the creature flees and all intellect devourers become hostile. On success, Us is lobotomised, which permanently reduces Intelligence and movement. If playing as The Dark Urge, the character has a different unique option.
Meeting Lae'zel
To advance to the next room, the party must follow the south-western path that leads outside. The party will encounter the githyanki soldier Lae'zel, who joins the party to escape. If Lae'zel was chosen as an origin character, Losiir will join the party instead.
As Lae'zel jumps from a ledge to attack, a telepathic connection between her and the player character causes her to realise that the player character is not under mind control. She insists on taking control of the Nautiloid at the Helm. To reach the Helm, the party needs to defeat three lesser imps.
There is a health restoring device at the northern side of the room at X: -39 Y: -376. To reach the next room, the party must continue north by climbing the arterial meshes.
Meeting Shadowheart
In the center of Shadowheart's room are two unconscious victims of the mind flayers, a high elf and human. The control panel adjacent to them has three sigils and buttons. The left panel is "Unleash", the middle is "Aggression", and the right is "Annihilate". "Unleash" causes psionic energy to radiate from the cultists while "Aggression" causes them to become hostile, initiating combat. "Annihilate" will kill both instantly. Selecting "Aggression" and defeating both enemies will reward 10 XP.
Toward the north-east side of the room, Shadowheart is trapped in a Mind Flayer pod. Interacting with Shadowheart initiates the quest 
. If Shadowheart was selected as an origin character, this pod will be empty. Warlocks, wizards, and sorcerers can free her by passing an Arcana Check on the contraption next to the pod. Barbarians can free her through passing a Strength Check. Otherwise, the party must head east to the Ceremorphosis Chamber to obtain an Eldritch Rune from a corpse on the far east side at X: 62 Y: -355. After opening the pod, the party can recruit Shadowheart or ignore her.
If the player character fails the DC 2 Wisdom check check to open the pod using the Eldritch Rune, they can try again using Lae'zel (or Losiir, if he is present). If both characters fail the check, Shadowheart remains trapped in the pod but can be found after the Prologue.
The locked 
Elaborate Reliquary at X: 7 Y: -361 can be opened with a 
Gold Key carried by the dead thrall at X: 31 Y: -355. Alternatively, the reliquary can be opened with a Sleight of Hand Check. If the party is attempting to retrieve the 
Everburn Blade in the next room without defeating its wielder (described in the next section), it is mandatory that at least one party member has prepared 
. Enemy reinforcements can be blocked from entering the room by placing several Cartilaginous Chests in the hallway right before entering the Helm near X: -12 Y: -389.
The Helm
When the party enters the Helm, their goal is to reach the transponder on the far west side of the room. A pair of lesser imps and a lesser hellsboar will block the path. A mind flayer will fight against Commander Zhalk, a powerful cambion wielding an Everburn Blade. The mind flayer is not initially hostile to the party because it believes them to be thralls; Zhalk, although technically hostile, will generally ignore the party to focus on the mind flayer.
The mind flayer corpses scattered throughout the room yield random gems. Other corpses can be looted for equipment and armour. Dotted around the room, including in the upper area, are 3 
Caustic Bulbs, 4 
Void Bulbs, and several 
Mucoid Shells and a 
Sodalite Shell.
Although the cutscenes and dialogue encourage the party to ignore Zhalk to reach the transponder, it is possible to kill him. Defeating Zhalk gives the party a large XP boost and the Everburn Blade. It is also possible to obtain the Everburn Blade by casting with Shadowheart or another character, forcing Zhalk to drop the weapon. Zhalk will continue to fight using unarmed attacks.
After several combat rounds, two cambion soldiers will enter the room through the east entrance. They are almost as powerful as Zhalk. To delay their arrival, it is possible to stack three Cartilaginous Chests in the narrow passageway just before the door to the Helm. This will delay the cambions from joining the fight as they are forced to attack the chests first to clear a path. If the chests are stacked at the start of this corridor (as far away from the actual door as possible) it is even possible that the cambions will not act at all if they have no direct path and no line of sight to anyone, effectively taking them out of the fight entirely. Note that the cambions can fly, and will use this ability to circumvent the chests if possible.
If Zhalk and all minor minions in the room are defeated before the two cambions arrive, the mind flayer will attack the party. If the cambions arrive while the mind flayer is still hostile to the party, the mind flayer will redirect its attention to the cambions. If the cambions defeat the mind flayer, the party gain XP as if they killed the mind flayer themselves. If the mind flayer does not become hostile toward the party but is defeated, no XP is awarded. This is true if the cambions or any other enemy lands the killing blow; however if the party kill the mind flayer using explosives, for example, the party is rewarded with the experience as if it was hostile.
When a party member (excluding Us) gets near the console, two lesser imps and a lesser hellsboar will appear and attack. If a character interacts with the console, the Prologue will end, regardless of any remaining enemies.
The Crash
Shortly before a party member connects the transponder, a red dragon latches onto the ship and breathes fire onto the console. The character at the console will connect the transponder and cause the ship to warp out of Avernus into the Prime Material Plane. As the ship appears in the sky, Nadira watches from behind a telescope with concern. Dror Ragzlin and Minthara also observe the ship's descent. They order a group of goblins to march out.
As the Nautiloid falls, the player character tries to hold onto the ship, but is struck by debris and sent flying. As the player character is about to plummet into the ground, they are suddenly held mid-air by a magical force. They land softly but lose consciousness until the next day.
Achievements
Descent From Avernus
Take control of the nautiloid and escape the Hells.
Devil's in the Details
Defeat Commander Zhalk on the nautiloid.