At launch, the game featured a total of ten Specialists, six of which (Ruin, Prophet, Battery, Seraph, Nomad, Firebreak) are returning characters from Black Ops III, while the other four (Recon, Ajax, Torque, Crash) are new additions.

Black Ops 4 features a new form of consumable items called Elixirs, which grant temporary buffs to the players upon activation; and Talismans, special modifiers that are applied at the start of each match.

The Multiplayer and Blackout modes take place in the 2040s, and are centered around the Specialists, a group of global elite soldiers hired by researcher Savannah Mason-Meyer (Evangeline Lilly), granddaughter of Alex Mason (Sam Worthington).

The initial Specialist roster includes: infantryman Donnie "Ruin" Walsh (Christian Rummel), demolitions expert Erin "Battery" Baker (Morla Gorrondona), Medical Sergeant Jarrah "Crash" Bazley (Mark Coles Smith), militia officer Kerk "Ajax" Rossouw (Stelio Savante), JGSDF soldier Katsumi "Recon" Kimura (Daisuke Tsuji), former British Army Corporal Kieran "Torque" Mackay (Matthew Waterson), ex-arsonist Krystof "Firebreak" Hejek (Adam Gifford), 54 Immortals enforcer He "Seraph" Zhen-Zhen (Judy Alice Lee), survivalist Tavo "Nomad" Rojas (David Cooley), and engineer David "Prophet" Wilkes (Dwane Walcott).

Additional Specialists later join the roster, including: hacker Leni "Zero" Vogel (Stephanie Lemelin), scoutswoman Alessandra "Outrider" Castillo (Loreni Delgado), assassin Spectre (Roger Garcia), and combat robot EWR-115 "Reaper" (Keith Silverstein).

Other characters featured in the Specialist Stories include: Jessica Mason-Green (Alexa Kahn), Savannah's sister and a former squad mate of Ruin and Battery; Sergeant Frank Woods (James C. Burns), Mason's best friend who appears as an instructor in the Specialists' training program; Viktor Reznov (Piotr Michael), a Red Army soldier who was Mason's ally prior to his death; and Raul Menendez (Kamar de los Reyes), former leader of the terrorist organization Cordis Die who plays a vital supporting role in Savannah's research.

The Chaos story of Zombies mode features a new cast of characters, starring: adventurer Scarlett Rhodes (Courtenay Taylor), former French Foreign Legion soldier Bruno Delacroix (Andrew Morgado), Mexican spy Diego Necalli (Christian Lanz), and British chemist Stanton Shaw (Nick Boraine).

Scarlett leads the other three in search of her father, Alistair (Charles Dennis), who has mysteriously disappeared following an encounter with the Order, an ancient cult worshiping a dark power led by the High Priest (Fred Tatasciore).

Dead of the Night, a prequel to Scarlett's story, features a different crew of characters, who are Alistair's associates: the Rhodes family butler Godfrey (Charles Dance), stage show cowboy Gideon Jones (Kiefer Sutherland), phony psychic Christina Fowler (Helena Bonham Carter), and Brigadier General Jonathan Warwick (Brian Blessed).

Other characters include the Oracle of Delphi (Cissy Jones), who guides Scarlett's crew toward their goal, and Perseus (Andrew Morgado), the demigod son of Zeus who became a zombie warlord after failing a trial.

The Aether story of Zombies mode continues the story from Black Ops III, and follows the Primis crew: Edward Richtofen (Nolan North), "Tank" Dempsey (Steve Blum), Nikolai Belinski (Fred Tatasciore), and Takeo Masaki (Tom Kane), as they continue their mission of securing their souls from fractured timelines at the behest of Doctor Monty, an omnipotent being who resides in the Agartha dimension.

Along their journey, Primis teams up with their original incarnation, known as Ultimis, while also receiving assistance from Victis, a group of survivors who previously interacted with Richtofen: Abigail "Misty" Briarton (Stephanie Lemelin), Marlton Johnson (Scott Menville), Samuel Stuhlinger (David Boat) and Russman (Keith Szarabajka).

Other characters include: the Shadowman (Robert Picardo), leader of the Apothicon race who opposes Monty and the Order of the Keepers; the Warden of Alcatraz Penitentiary (Tom Kane), who subjected himself to becoming the Shadowman's servant and is tasked with imprisoning Primis; Doctor Ludvig Maxis (Fred Tatasciore), an ally of Primis from Dimension 63 who attempts to contact them occasionally from Agartha; Samantha Maxis (Julie Nathanson), Ludvig's daughter from the original dimension who now also resides in Agartha as a cleansed soul; Eddie, the cleansed soul of Richtofen from Dimension 2210 who now resides in Agartha in the form of a child; Rushmore (John de Lancie), an artificial intelligence operating the systems of Camp Edward, a Broken Arrow facility; Cornelius Pernell, Broken Arrow's Director who was transformed into a pure electric being following an experiment; and Pablo Marinus, a Mexican test subject of Group 935 who lives in their Siberian outpost as a hermit.

In 2043, during a covert mission involving a mercenary group, US Army Specialist Jessica Mason-Green is presumably killed in action while her squad mates, Donnie "Ruin" Walsh and Erin "Battery" Baker, escape with critical injuries.

Two years later, Savannah Mason-Meyer, a trillionaire researcher and Jessica's sister, recruits ten of the world's most elite soldiers, including Ruin and Battery, for a top-secret project against an unknown threat.

After inhaling a mysterious vapor, they begin to hallucinate and are taken back in time to an Gladiatorial Arena in Roman Egypt, where the High Priest of Chaos ses a Sentinel Artifact to turn slaves into zombies and pit them against gladiators for entertainment.

During their mission to secure their own souls, the Primis crew takes a detour to Alcatraz Island, where Edward Richtofen plans to acquire blood vials, items he deems necessary for his "insurance policy", to protect his companions.

Through their attempt to survive his wrath, Primis learns that the Warden, working for the ancient Apothicon race via the Shadowman, intends to use Richtofen's blood to power a special machine called the Dark Mechanism, due to it containing a massive amount of Aether energy.

Having broken the cycle, Richtofen hands the Kronorium to Nikolai Belinski and passes over the leadership mantle, convincing the latter that his soul is needed to defeat the omnipotent Doctor Monty.

Meanwhile, at the Ascension Facility in Russia, the scientist Yuri Zavoyski tricks his partner Gersh into activating a black hole device, sucking him in it, per the orders of a corrupted Samantha Maxis.

Primis and Ultimis travel together to Camp Edward, a nuclear testing facility run by the American research group Broken Arrow, in search of an Elemental Shard.

At the Siberian outpost, Victis encounters Pablo Marinus, one of Richtofen's former test subjects who was assumed to have died, and receives his help in constructing the device, using the blood of an ancient Apothicon being, a container dubbed the Seal of Duality, and the Elemental Shard.

Combined with publisher Activision's decision to release the game in October, the team resorted to creating the Blackout battle royale mode as a replacement for the traditional campaign.

Gameplay would include PVP and PVE sections, abilities similar to those from Black Ops III, side-objectives, and companion characters based on the same game's multiplayer specialists.

[36] In an interview with Polygon in May 2018, Bunting later claimed that a traditional campaign for the game had never been intended, and appeared to repudiate earlier reports that Treyarch had scrapped work on it due to time constraints.

[38][39][40] In its 9.5/10 review, Game Informer wrote: "Call of Duty: Black Ops 4 makes a sacrifice that's sure to be off-putting to some with the lack of a campaign, but the surrender of tradition comes with sweeping and significant benefits.

[50][51] Several weeks after Black Ops 4's release, a microtransaction system allowing for the purchase of cosmetic items which provided no gameplay advantages was incorporated into the game, drawing criticism for being overpriced while offering few benefits in return.

He lamented that it felt the "fantastic" core game was buckling under pressure to generate more money for Activision, citing its additional season pass, Black Market Contraband, and paid-for cosmetics, and called the overall design "convoluted, confused and inescapably money-grabbing".

[56] Kain echoed these complaints, further criticizing the cost of loot boxes and only being available by paying real-world funds, saying "There are so many ways you can spend your money in Black Ops 4 at this point, it's just ridiculous."

[57] As a result of the loot boxes, some fans also accused developer Treyarch's design chief David Vonderhaar of lying as he had initially stated that unlocking Blackout characters could not be achieved through microtransactions.