Utilizing the titular Astral Chain, the twins restrain and tether the creatures, employing them in combat and investigation, referring to them as Legions.

[1] Exploring the world, questioning non-playable characters, and examining evidence yields clues and logic puzzles that become leads which further the investigation process.

Combat takes place in real-time, both melee and ranged weapons are used to fight enemies, primarily malevolent creatures called chimeras.

The player is also able to utilize the chain in order to zip line out of danger through enemy crowds, as well as crossing gaps and bottomless pits between buildings and platforms.

Completing combos, interrupting enemy attacks, restraining enemies, dodging, and deploying a Legion at the correct moment will offer the player a chance to perform a sync attack,[4] requiring the player to press the left trigger at the right instant, similar to a quick time event.

Early in the game players unlock the IRIS tool, a heads up display from which they can inspect the environment and search for clues, as well as save their progress, manage the inventory, customize in-game menus, view the level map, and manage orders (benchmarks and photo challenges that reward the player with items, crafting materials, XP, money, and photo filters).

The world is under attack by lifeforms called chimeras, which are normally invisible, and reside in the Astral Plane, an alternate dimension composed of crystallized data that is uninhabitable to humans.

The chimeras cause destruction, drag civilians into the Astral Plane via wormholes called gates, and spread "red matter" that "redshifts" living things, corrupting humans into aberrations.

The Neuron officers are also assisted by a hacker named Harold "Hal" Clark, who pilots a modified field drone.

Their first investigation mission goes awry when the Legionis ends up being pulled into the Astral Plane, causing the rest of the squad to pursue them in through the gate to save them.

As prolonged time in the Astral Plane redshifts humans, the Neuron officers grow weak and lose control over their Legions, causing them to break free and go berserk.

During this time, the twins come into contact with Dr. Jena Anderson, a former pupil of Yoseph's who is instigating chimera attacks and bears a grudge against the UNION, the Ark's ruling government.

After visiting a comatose but recovering Akira at the ARI, the Legionis finds out from Jena that the circumstances of their birth during the Pandemic nearly twenty years before are the reason why they have such control over their Legion.

The Legionis goes undercover and explores Zone 09 with Hal, discovering that UNION developed a drug called Blue Evolve that could allow humans to fight chimeras, which carried the side effect of turning the users into aberrations, causing the Pandemic.

After battling one of Jena's chimeric homunculi, they are saved by a recovered Akira, clad in black armor and fighting with a new Legion, their control over it now on par with the Legionis' abilities.

Yoseph then calls in the Ravens—a newly created task force of Legion users—and orders them to kill the Legionis, causing them to fall off an overpass.

The Legionis wakes up back in human form, having been rescued by Hal and Olive, and brought into a hiding place in Zone 09.

Hal explains that Yoseph has largely replaced Neuron with the Ravens and is actively hunting the Legionis, accusing them of treason.

He uses the clones as a catalyst to create the ultimate Legion, Noah, and merges himself with it, intending to absorb all remaining life on Earth in order to become a god.

Following Noah's destruction, chimera attacks begin to decrease drastically, allowing humans to consider leaving the Ark and reclaiming the rest of Earth.

Alicia and Jin put Neuron back together, with Olive as interim commander, and the task force continues to handle the few chimera attacks that still occur on the Ark.

[11] While the ability to play as male or female was always intended as an option, the game initially did not feature twin protagonists in the project's early stages.

Taura noted that the main difference in approach compared to PlatinumGames' work on Nier: Automata was that Astral Chain had its scenario built around the gameplay rather than the other way around.

[11] When asked about the possibility of Astral Chain becoming available on multiple platforms in a February 2020 interview (focused on the then-recently announced Kickstarter campaign for the remastered The Wonderful 101), Inaba stated that "it's too early to say", and that "ultimately, it's Nintendo's call, not [theirs]".

[12] Fans had later noted in January 2021 that the game's copyright notice on PlatinumGames' website had changed to show Nintendo having full ownership of the title, despite previous claims that the property was co-owned.

[15] Nintendo proposed to PlatinumGames the idea of partnering with Avex Group to acquire vocalists for the game's theme songs.

"[29] Steven Petite of IGN praised the combat, commenting that "though Astral Chain lacks a deep combo system, it makes up for that and then some with its roster of Legions".