President Benford is introduced, planning on revealing the truth about the Raccoon City incident, bringing this up to Leon, who he conforms in as a valued friend. He is briefly seen consuming a body as a zombie before turning on Leon and Helena, who kill him.
Helena believes the incident to be her fault (take note that she is a member of the Secret Service, and thus responsible for his safety). As she says this, other places in Tall Oaks are shown to be damaged, suggesting that an outbreak has taken full-swing. We then see Leon walking through Tall Oaks Station, and a horde of zombies running to him from further down the underground area. The scene cuts back to Leon in the university, responding to Helena - "what are you talking about?"
In the next section, we see a crashed bus in an afforested area with its headlights on, allowing us to see a number of zombies approach it. Skipping to a shot from inside a government building, Hunnigan informs Leon that 90% of Tall Oaks' populace has been infected with the unnamed virus, equating to over 70,000 hostiles. We see a person extend their arm from the bus, trying to get out. It then explodes in front of Leon. Leon's response in the Hunnigan scene is a comparison between the current outbreak and Raccoon City's.
A series of shots continue, showing Leon fighting varius agile zombies, ending with him back on the subway tracks as a train rushes toward him. In the Tall Oaks cathedral, Leon asks Helena what is inside a particular room, to which she responds that it's better if she just shows him.
The scene then cuts to Chris Redfield as he rides a BSAA helicopter over the Chinese city of Lanshiang. He monologues over how she can't keep "running away" from a then-unspecified event (later revealed to be regarding an incident six months prior where men under his command perished). He is shown moving through the large city as civilians flee in terror. A radio contact informs his unit - the BSAA Alpha Team - that they are to approach Point Ace of Spades while suppressing the outbreak, which they believe/know to be caused by bioterrorists. We see shots of the unit breaking open a metal door, and a J'avo inside a room mutating to grow an extended arm. Military vehicles are then seen being blown up on the streets, accompanied by Chris radioing in to headquarters, informing them that the extent of the outbreak is "worse than we thought." Chris is then seen firing at armed men - likely J'avo. More scenes cut by quickly, including a helicopter flyng dangerously-close to Chris and more mutations. Alongside a clip of a J'avo is Chris saying "it's regenerating".
We are now introduced to Jake Muller as he stands in front of a heavy-lift tandem-rotor helicopter (which appears to be a Boeing CH-47 Chinook) in Edonia. He says "I want 200,000 up front; another 200 when this is over... Oh, the B.O.W.s? Those are extra." As he says this, we are shown Jake's impressive combat skills; Sherry Birkin and the Ustanak. A combat helicopter is also seen firing a missile toward Jake, perhaps trying to kill him - he survives the blast. The Ustanak is then seen crashing into an underground room from the ceiling, then running after Jake and Sherry down long passageways. Jake is then heard saying "I was better off as a mercenary", informing us of his occupation. Sherry helps Jake up, saying "I'm not gonna let anything happen to you; the world needs you!" We then see them running and jumping across the rooftops of Edonia, with the Ustanak in hot-pursuit.
The scene cuts again. Jake is seen with some sort of medical equipment, either injecting himself with a chemical or extracting a sample. His voice says "Oh, no, not me - just me blood. Well, the world can have it, as long as someone ponies up the dough." This suggests that someone is after him, knowing that his blood carries something important. We then see BSAA agents rush through a room in Edonia. We see a few members being forced to the ground, convulsing - one person catches fire. A "needle bomb" is seen flying through the air, followed by a shot of an operative being essentially devoured by the Chrysalid he is turning into. Chris looks in horror as one explodes. We hear Chris talking - "after what she's done to us, how many of us are dead because of that bitch!?", implying that an antagonistic woman is involved with his men's deaths. We are now shown Piers Nivans, who previously appeared in a Manga series. He pushes Chris back, saying "I'm right with you Captain, but your personal vendetta isn't gonna get us anywhere!", suggesting a link between Chris' speech; his men's death, and the line from earlier in the trailer.
In the next shot, we see a man riding inside of a tank as it pushes through Edonia. Following that is a computer tablet displaying images of victims of the outbreak. After this is gameplay footage of Chris jumping to the ground to get in cover, only for a J'avo's elongated arm to pull him out of it. Over the next few seconds we see scene after scene of the playable characters being attacked by either J'avo or zombies, followed by them attacking their enemies.
At the end we see more "dramatic" scenes, such as Jake catching Sherry on a motorcycle in Lanshiang, and him jumping onto a helicopter, along with brief footage of a gigantic creature roaming Edonia.