Dr. Maxis and his scientist team, Group 935, were tasked with creating an army of super soldiers and new technology for the government project christened "Der Riese" or "The Giant". In his experiments, Maxis used Element 115 to create the zombies. The zombies, however, couldn't be controlled and would always be killed when they went berserk. While this was going on, Richtofen was testing 115 on living test subjects to create his super soldiers at a Siberian facility. In his experiments, Richtofen used Takeo, Nikolai Belinski, and an unknown Mexican. When Richtofen accidentally killed the Mexican, he replaced him with Dempsey. Dempsey had recently been captured when he led a Marine Recon team to an abandoned asylum to rescue Dr. Peter McCain, an OSS spy sent to infiltrate Group 935. Peter, however, had already been discovered, along with Harvey Yena. The testing affected each of the subjects' minds, making Dempsey extremely aggressive, quieting Takeo into only reciting Japanese proverbs, and making Nikolai functionless without vodka. It also had the side effect of erasing their memories, although, some still possess a few memories.
The new weapons Group 935 created were also powered by 115. Maxis created the Ray Gun based on plans received from Shi No Numa. Richtofen created the Monkey Bomb and Wunderwaffe DG-2 from 115. Maxis promised to mass-produce the DG-2 to his superiors, but his growing infatuation with Sophia slowed his progress and infuriated Richtofen, who then plotted to overthrow him and take control of Group 935.

Maxis also created 115-powered teleporters, but they would always destroy anything sent through them. All of these experiments were done with his assistant, Dr. Richtofen. When he used his daughter Samantha's dog, Fluffy, as a teleporter test subject, he accidentally created the first hellhound. The dog was teleported, but instead of being destroyed like the past test subjects, she was zombified. When Samantha came running in and started questioning her dad about her dog, Richtofen left the room. Richtofen then followed through with his previously-planned betrayal by locking Maxis and his daughter in the room with the hellhound, which apparently killed Maxis and Samantha. Richtofen then proceeded to cover up his betrayal and unleashed the zombies.

Richtofen then took his super-soldiers to Shi No Numa. After this was done, the group went to Der Riese, which had been abandoned since the zombie takeover. The group used the Wunderwaffe DG-2's 115 to overcharge the Teleporter, making it capable of time travel. Richtofen was apparently unaware of this possibility until he tried it. He seems unconcerned that he and his partners have been teleported to an abandoned theater in Germany in an unknown year. Although he didn't know what year it was, Richtofen knew about the theater as it was the place Maxis would unveil the Teleporter to the German high command. Since Maxis was killed, the theater was abandoned.

Sometime prior to Ascension, Yuri Kravcheski was transferred to work on sending monkeys into space, much to his dismay. His transfer was caused by his superior, Gersch, who he holds a grudge against. As the radio messages progress, Yuri notices the teddy bear and the Matryoshka dolls and wonders how a child could be let into the station. A child then slowly drives Yuri insane. Yuri, in his state of insanity, finishes the Gersch Device and has Gersch activate it, letting in the zombies and trapping Gersch. Yuri soon realizes his mistake and is heard screaming at the end of the last recording.

After the events of Kino der Toten, the main characters somehow reach the abandoned Soviet launch pad in Ascension. When the game starts, the four are landing in the starting room on the lunar lander as the color turns to black and white (which the characters acknowledge). The characters then hear Gersch, who tells them that the mechanism must be repaired. He is referring to the Kassimir Mechanism, which must be repaired by completing different tasks. After all of the tasks are completed and the mechanism is repaired, Gersch is free and gives the characters 90-second death machines.

While the events of Ascension are occurring in Russia, the events of "Five" are also unfolding in the Pentagon. A piece of Intel reveals that all Wunderwaffe materials were to be moved to American-controlled installations. As a mainframe is visible behind one of the windows in "Five", it is apparent that it was moved there as per this order. While John F. Kennedy, Robert McNamara, Fidel Castro, and Richard Nixon are negotiating, zombies break into the Pentagon with only the four of them left to fight them. While fighting, they call the characters in Ascension using three red telephones spread across the Pentagon.

As they continue fighting, the three super-soldier test subjects slowly regain their memories. Takeo is the first to remember, and remarks to himself that some day when the group is finished fighting zombies Richtofen will get what he deserves. He also shows his observations of the other two. He believes Nikolai drinks vodka because he wishes to forget the past and can't function when he remembers it, perhaps meaning Nikolai is beyond hope. Tank, on the other hand, is slowly making progress, as he remembers that he'd seen Richtofen before the fight at Shi No Numa. Takeo notes has shifting memories and believes Tank is finally remembering what Richtofen did to him.

Sometime in the present, George A. Romero stumbled upon Group 935's research while making a WWII film. He and the cast took a ship out to an abandoned lab in Siberia. After he and the ship's crew were zombified, only the cast, made up of Sarah Michelle Gellar, Robert Englund, Danny Trejo, and Michael Rooker, remained. This set the stage for Call of the Dead. After the Kassimir Mechanism was completed in Ascension, it overloaded the teleporter and sent the original characters to a Group 935 facility in Siberia, where they were trapped behind a locked door. The celebrities then helped them escape to Paradise. Escaping wasn't Richtofen's only goal, however, as he meant to travel to the Siberian facility to obtain the Golden Rod, which the celebrities found for him without knowing any better. Richtofen thanks the group by giving them the DG-2 to help them fight the zombies. In reality, the group could've escaped after the security system was disabled. It is unknown what became of the celebrities after helping the group escape.

Shangri-La, however, does not live up to its name, as its inhabitants have all been zombified before the group's arrival. Richtofen states that this is the last step to controlling the world before he is teleported there. The temple houses a mining facility filled with Element 115, explaining the inhabitants' zombification.

Prior to the group's arrival to Shangri-La, two explorers, Brock and Gary went on an expedition to prove their theories on Argatha. Brock later figures out that the temple wasn't built by an ancient civilization, but by people in the modern era interpreting it. After investigating the temple, the pair accidentally activated the temple's time travel and died in the resulting Zombie attack. The group travels back in time and helps the pair survive. The pair's changing fate is illustrated by the radio that changes message and location as the group helps them. When the group finally create the Focusing Stone, it lands on an altar with Richtofen's name on it, meaning the temple was in fact another Group 935 facility and explaining Richtofen's knowledge of its location. The two explorers are then sent back to the moment they discovered the temple, indicating that they're stuck in a never-ending loop.

Now in possession of both the Golden Rod and the Focusing Stone, Richtofen believes he can now control the zombies. The group then travels to area 51 so they can get to the moon via a teleporter to a top-secret Moon facility. Due to the Element 115 on the moon, astronauts and scientists sent there have been zombified before the group's arrival. Richtofen then has the group complete the device (which has been built in the form of an ancient pyramid). When the device is completed, it opens up to reveal Samantha Maxis suspended in the air. As it turns out, the device acts like a prison and keeps her cryogenically frozen so she can be used to control the zombies. Richtofen goes to a terminal to power up the Golden Rod (or V Device) and the Focusing Stone, which he fuses together. However, he encounters Dr. Maxis inside the terminal, who tries to stop him. Richtofen switches souls with Samantha Maxis to gain control of the zombies. Richtofen finally thinks everything has gone his way, until Takeo, Tank, and Nikolai decide to stop him. Dr. Maxis, sensing Richtofen's betrayal, prepared a backup plan in case Richtofen got this far. (He even referred to Richtofen by name in his radio message.) The group fires the missiles located on the moon and blows up the earth.