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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, ending up in Avernus, the first of the Nine Hells. The objective of the Prologue is to find a way out of the Nautiloid, ideally not by dropping down into Hell.
Objectives
Walkthrough
Nursery room
This is the room in which the game begins. The player character breaks free from a Mind Flayer Pod and stands alone in the room. There are various empty mind flayer pods around the room indicating that there might be other survivors.
In the middle of the room is a mind flayer "nursery" i.e. a pool filled with larvae. Passing an Investigation check will reveal that it is about to break apart. If trying to touch the "nursery", it explodes and causes a small amount of damage. To the south of the "nursery" is a dead mind flayer that can be looted for a random gem.
Farther south, it's possible to climb to a small elevation in the room, where a 
Cartilaginous Chest which contains some random loot including gold.
To the east of the room, slightly southward, there is a larger elevated area, circling around all the way to the northwest of the room. There ar n 
Onyx and a 
Rune Slate lying on a table. Interacting with the slate confers visions of the Nautiloid ship. A Cartilaginous Chest in the rooms contains some gold.
On the west side of the room, there is an illithid restoration device that fully heals any party member upon interaction, and a door to the next room.
Brain room
In the northeast there is a table with an Illithid Record and a Goblin corpse with a little gold. The record can be interacted with to reveal that it contains knowledge about Goblin culture. West of the goblin is a table with three additional rune slates, which give further insight about the Nautiloid and a comment about an anomaly, likely referring to the player character.
Westwards and to the north of the room is a table with an Eldritch Tablet. The tablet can be interacted with to reveal that it contains knowledge about humanoid history (elves, dwarves, humans, etc.).
In the middle of the room, a small elevator to an upper section of the room. A dying person sits on a chair with their scalp removed, their exposed brain telepathically asking for help.
The Intellect Devourer
If interacting with the person in the chair, the player character can notice by succeeding an Arcana Check that the exposed brain is not in fact the person's own brain, but rather an Intellect Devourer named Us. There are various options to try to free the creature from the skull, and it's also possible to leave it in place or destroy it outright. If choosing to free Us can give a bit of information about the situation and will become a temporary Companion.
While freeing the intellect devourer from the skull, there is also the option to mutilate it to make it more obedient. Howewever, this seems unnecessary as it's obedient to either way. Us will become hostile if attacking any non-hostile creatures while on the Nautiloid unless its was lobotomised. Failing the Dexterity Check while trying to mutilate it will cause the creature to become hostile, too.
If freeing Us and ensuring it survives the Prologue, it will reappear in Act 2.
Meeting Lae'zel
To the west of the brain room there's an opening in the Nautiloid's shell. An outer path leads northwest, where the Githyanki soldier Lae'zel can be encountered, who was previously seen being infected with a tadpole in the opening cinematic. If Lae'zel was chosen as Origin, Losiir will be met instead.
As Lae'zel jumps down from a ledge to attack, the telepathic connection between her and the player character caused by the mind flayer tadpole makes her realize that the player character is not under mind control, and that cooperation wood be wise. She insists to go to the helm of the Nautiloid, where it's possible to take control of it, but first it's necesssary to clear the way by battling three imps.
This is easily done by going on the offense. They drop 
Scimitar, 
Handaxe and 
Light Crossbow.
After the battle, you can loot a dead incinerated Mind Flayer, two imp corpses and four dead thralls for minor loot, including another Handaxe and Light Crossbow as well as 
Shortsword, 
Simple Robe and 
Potion of Healing.
The incinerated mindflayer corpse has a 
Potion of Speed.
the exit of this room is to the northeast, after climbing some cliffs. There's a healing pod on the ascent.
Meeting Shadowheart
In this room you will be greeted by a pair of knocked out cultists on chairs, and some sort of control panel with three pairs of sigils and buttons. Lae'zel will warn not to touch anything.
If interacting with the sigils on the control panel each will trigger an Arcana Check to allow to read it. The left one says "Unleash," the middle one "Aggression," and the right one "Annihilate". The Unleash button apparently makes psionic energy radiate from the two knocked out cultists, but it's unclear what use this has because it does not allow to talk to them. The Aggression button will make them become hostile. The Annihilate button will kill them instantly. Making them attack and then defeating them gives 10 XP each.
The party also hear a woman trapped in a mind flayer pod thudding against its glass encasing. She's Shadowheart, who will suggest using the contraption next to the pod to get it opened. Interacting with the contraption will reveal that there is an empty socket of some sort. There is an object needed to fit in there, the Eldritch Rune from the next room to the north.
Shadowheart's pod can be opened by inserting the Eldritch Rune in the empy socket. Warlocks, Wizards or Sorcerers can free her without using the rune by passing an Arcana Check on the machine. Barbarians can free her without using the rune by passing a Strength Check on the pod.
With Lae'zel as a companion, Shadowheart will be a little snarky, but either way she asks to join the party as a Companion.
There is a backpack with gold and a random gem. If Shadowheart is chosen as Origin, this pod will be empty and there will be no way to open it.
To the south, there's a table with various objects on it: a 
Burnished Necklace, a 
Dark Mind (a brain in a jar), an Illithid Manuscript, which seems to tell a story about "a brain, a githyanki warrior, and centuries of darkness", and a locked 
Elaborate Reliquary. The lock of the reliquary can be lockpicked. Otherwise it's possible to look for the key. It contains gold and an Onyx.
An intellect devourer occasionally walks through this room. The intellect devourer won't drop any loot if it is killed. If choosing to attack this intellect devourer for the extra XP, then Us will attack at will, unless it was successfully mutilated.
At the entrance of the next room to the north, the ceremorphosis room, lies a dead thrall on which the Gilded Key can be found, which opens the reliquary in the previous room. There is yet another mind flayer pod at the center of the ceremorphosis room. This one contains a dazed woman who seems to be unresponsive. Behind her is a console with a sigil and a button. The sigil triggers an Arcana check, and succeeding it reveals that it says "Perfect". Pushing it, transforms the woman in the pod into a mind flayer.
On a raised platform at the back of the room there is a cartilaginous chest with 2 Potions of Healing and another dead thrall with an Eldritch Rune, which can be inserted into the control panel of Shadowheart's pod back in the previous room to free her.
There's nowhere to go from this room but back to the previous room.
The Helm of the Nautiloid
If entering the helm, the party can watch a mind flayer fighting Commander Zhalk, a powerful Cambion wielding the flaming greatsword, the Everburn Blade. A cutscene will play in which the mind flayer orders the party to connect the nerves of the transponder, referring to the control apparatus of the ship that allows it to travel between dimensions. The mind flayer thinks that the party are thralls, thus considers them an allies.
A pair of lesser imps and a Lesser Hellsboar will block the path. One of the imps carries a Light Crossbow, the other Scimitar.
There are also lots of dead bodies on the floor. A dead thrall can be looted for a 
Leather Armour and Shortsword, serveral dead imps have a Light Crossbow, a Handaxe and 
Dagger and two more thralls have Shortswords. Two mindflayer corpses yield random gems.
Dotted around the room are 3 
Caustic Bulbs and 4 
Void Bulbs, lying on tables (some in an upper area of the room), but it's probably not worth chasing after them. There are some 
Mucoid Shells and a 
Sodalite Shell as well.
While all the cutscenes and dialogue in this scene of the game tell the party to ignore Commander Zhalk and reach the console, it's actually possible to help the mind flayer kill him. This gives the party a large XP boost, and he will drop the 
Everburn Blade. It is possible to obtain the Everburn Blade without or before killing Commander Zhalk by using 
from Shadowheart.
After a couple of combat rounds two Cambion soldiers will enter the room to join the fight. They are almost as powerful as Commander Zhalk himself. It is possible to stack the three Cartilaginous Chests found around the nautiloid in front of the area where it is narrows just before the door to the Helm. This will block the two Cambions from joining the fight as they will be forced to attack the chests to clear a path, and since they have a high damage resistance it will take some time for them to do so.
If killing Zhalk (along with all the minor minions in the room) before the other two cambions appear, the mind flayer will become hostile, saying "you are no longer needed," and attacks the party. If getting the timing just right, the two cambions should arrive right after that and the mind flayer will focus on them instead. The cambions may kill it, providing the party XP as if they killed mind flayer themselves. If the cambions arrive before Zhalk dies, the mind flayer doesn't turn hostile, thus its death doesn't provide any XP.
If nearing the console, then another two lesser imps and another lesser hellsboar will appear. Once reaching the console, interacting with it will start a cutscene and end the prologue.
The Crash
In the cutscene that follows, the character that interacted with the neural console connects two arms to make the ship warp out of Avernus and back into the Prime Material Plane, but moments before the warp a red dragon latches on to the ship and breathes fire onto the console.
As the ship appears in the sky of the Material Plane, a Tiefling behind a telescope (Nadira) is seen looking at it with worry, and at another place, a Hobgoblin (Dror Ragzlin) and a rather smug-looking Drow (Minthara) observe the ship's descent. They order a group of goblins to march out of some sort of fort they seem to be occupying.
Back in the crashing Nautiloid, the player character is trying to hold on, but is hit in the face by a piece of debris and sent flying out of the Nautiloid. As the player character falls to the ground, moments before the impact they are held mid-air by magical force and end up having a soft landing.
Achievements
Descent From Avernus
Take control of the nautiloid and escape the Hells.
Devil's in the Details
Defeat Commander Zhalk on the nautiloid.