The film starts with a woman named Malorie Hayes (Sandra Bullock) telling two kids, known only as Boy (Julian Edwards) and Girl (Vivien Lyra Blair), that they are going to take a dangerous trip across the water, and she stresses how urgent it is that they keep their blindfolds on as they head outside. Malorie grabs a box with her pet birds inside and guides the kids outside by following a string trail before finding the boat and hopping in on the river.
Five years earlier.
Malorie is an artist who is pregnant. She is visited by her sister Jessica (Sarah Paulson), and the two watch a news report on unexplained mass suicides that started in Siberia and is now spreading across Europe. Jess notices Malorie's painting, which she says symbolizes a lack of connection, but Jess tells her that it won't be like that with the baby. She then offers to escort Malorie to the doctor.
Malorie visits Dr. Lapham (Parminder Nagra) and makes jokes with Jess about drinking while pregnant. Lapham doesn't find the comments too humorous and offers Malorie an alternative to let someone adopt the baby if she feels she isn't ready to raise it. On their way out of the office, Malorie and Jess notice a woman they passed earlier now acting erratic and banging her head against the glass window. They realize that whatever was affecting people in Europe and Siberia has now arrived in America. They run outside just as the chaos is happening, with people crashing their cars in the street. Jess drives Malorie away, but not long after, Jess's eyes turn a weird color as she starts to appear frightened by something only she can see. She drives frantically, with Malorie trying to keep her on the road, but Jess flips the car and crashes. They survive, but Jess is still under a trance, and Malorie can only watch as her sister steps in front of a truck.
Malorie runs along with everyone else. She is knocked over and falls in front of a house. A woman named Lydia (Rebecca Pidgeon) steps out of her house to go help Malorie, even as her husband Douglas (John Malkovich) objects to it. Before Lydia can help Malorie up, she appears to go into a trance and seems to be talking to her mother. Lydia walks into a burning car that soon explodes. A man named Tom (Trevante Rhodes) helps Malorie up and runs into the house. They are followed by a cop named Lucy (Rosa Salazar). Also in the house are Greg (BD Wong), the homeowner, Charlie (Lil Rel Howery), Felix (Machine Gun Kelly), Cheryl (Jackie Weaver), and a couple named Jason (Taylor Handley) and Samantha (Amy Gumenick). The latter two flee the house when they hear their son over the phone sounding like he's in danger.
The other people all tell each other what they have seen in those who have been afflicted by this mysterious force. Charlie suspects that the entity is caused by demons that take the form of one's deepest sadness or greatest loss. They all realize that the entity is invisible and that looking at it will cause one to commit suicide. Malorie steps away from the group, and Tom goes to comfort her as she tells him what happened to Jess. The group then boards up the doors and place newspapers on the windows to prevent anyone from looking outside.
In the present day, after six hours on the river, Malorie and the children continue to go down the river as it is now pitch black. Malorie makes attempts to contact people over the radio, and she starts to hear the entity whispering her name.
Back in the past, a survivor named Olympia (Danielle Macdonald) pleads to be let in the house. Douglas tries to prevent this, but Malorie grabs a rifle just in case. The others carefully allow Olympia into the house, and they see that she is also pregnant. Greg then offers to observe whatever is outside by checking out the transmitters in the house. He sits in front of the computers waiting to see something on the monitors, and then it looks as though he does. And then the others hear a thumping coming from the room. They rush upstairs in time to see Greg tip himself over and smash his head against an edge, killing him. The others then destroy the computer monitor.
Later that night, Olympia tries to talk with Malorie over their potential baby names, but Malorie just wants to be left alone. She walks around and thinks she hears a thumping noise in the house, but she finds it's just Lucy and Felix hooking up.
Fourteen hours on the river.
Malorie hears the voice of a man (Happy Anderson) calling out and saying it's safe to take the blindfolds off, but Malorie orders the kids not to do so. He claims he has food and that he has seen the entity, saying there's no reason to be scared of it. Malorie takes out her gun and fires blindly, just before the man attacks her and tries to take her blindfold off. Malorie fights the man and kills him by hacking at him with a machete.
Back in the past, the group has begun to run out of food, and they know help isn't coming. Malorie, Tom, Douglas, Lucy, and Charlie get together to go to the supermarket where Charlie used to work since he locked the place up as things went sideways. They paint over the windows and use the GPS to guide them. On the road, they feel that they are driving over dead bodies and try to ignore it. The GPS then starts going off over a proximity alert, meaning the entity is surrounding them. Tom manages to drive them out of harm's way. They get to the market and grab as much food as they can. Malorie sees some birds that she decides to take with her as pets. Suddenly, they hear the voice of Charlie's co-worker Fish Fingers (Matt Leonard) locked in a freezer and begging to be let out. He then starts going on about how the entity is beautiful and must be seen. Fish Fingers starts to break out while Lucy, Tom, and Douglas try to hold him back. Charlie then sees the entity and realizes he is doomed. He charges toward Fish Fingers and has them both shut in the freezer where Charlie dies, letting the others return home. Fish Fingers' voice is still heard begging to be let out.
That night, Malorie briefly bonds with Douglas over their personal problems. The others then hear what sounds like the car being driven away. They go into the garage and find that it's gone, and so are Lucy and Felix.
24 hours on the river
Malorie stops rowing to take a break. When she resumes, she bumps the boat into a sunken truck, and Boy falls out of the boat, but Malorie pulls him out and tries to warm him, but the food and blankets have fallen into the river, so she does her best to warm Boy up. She leaves the kids in the boat as she heads into the woods to try and gather food. Malorie enters a building where she hears a noise and sees things moving on their own, being pulled by the entity. She manages to make her way out of the building, but the entity continues to whisper her name. Malorie fires her gun at the unseen entity, which Girl hears and so she leaves the boat to help Malorie, but she finds Girl and grabs her, scolding her for leaving the boat as they return to it.
In the past, Tom tells Malorie about how he was stationed in Iraq, and he and his comrades would follow a man as he was escorting his kids to school in the middle of all the chaos. The two of them also start to develop feelings for each other.
Olympia lets a desperate man named Gary (Tom Hollander) into the house. The others aggressively search and interrogate Gary. He tells the others that some escaped mental patients came after him and his friend, forcing the two of them to look at the creatures. Gary's friend fought one of them, allowing him to get away and run to the house. He says there are also people outside not wearing blindfolds, willingly trying to see the creatures and wanting others to see them. Douglas doesn't trust Gary and tries to force him out of the house at gunpoint, but Cheryl knocks him out and lets Gary stay, and they lock Douglas in the garage. Olympia tearfully apologizes for letting Gary in and says she feels like a burden, but Malorie tells her she isn't. Olympia then asks Malorie to take care of her baby if something happens to her, and Malorie agrees. She then gives Olympia a Hello Kitty toy to give the baby.
38 hours on the river
We see Girl holding the Hello Kitty toy, indicating she is Olympia's daughter. Malorie gets herself and the kids under a blanket to warn them that they are approaching the rapids, and that it will be the most dangerous part of the journey. She tells them that somebody is going to have to have their eyes open to navigate, and both kids volunteer, but Malorie decides it's not worth sacrificing either of them, so she says nobody will look, and they will just brave the rapids with blindfolds.
Both Malorie and Olympia begin to go into labor. While Tom and Cheryl help the women, Gary takes out a bunch of drawings of the creatures, as he is one of the crazy people who has seen them and wants others to see them. He takes Malorie's birds and puts them in the fridge (since they appear to sense and alert others to danger) before tearing the papers off the windows, which Douglas observes. Gary opens the garage door to try and get rid of Douglas. Meanwhile, Olympia gives birth to a girl while Malorie gives birth to a boy. Gary enters the room and pulls the blinds up in front of Olympia. She hands Malorie her baby right before she jumps out the window. Gary then forces Cheryl to open her eyes to the outside, causing her to kill herself with scissors. Douglas comes in with the rifle, but cannot shoot with his eyes open and is afraid to hit Malorie and the babies. He manages to shoot Gary in the arm, but he kills Douglas by stabbing him with the scissors. Tom then sees the rifle and tries to grab it, as does Gary. Two gunshots are heard, but Tom is seen alive going to be with Malorie and the babies.
It is now five years later, just before the start of the film. Malorie and Tom have been living together, raising the two kids, but Tom calls Malorie out for not connecting with them or even giving them names. They hear something outside, and it's some people driving their cars out with no blindfolds or covers on the windows. Malorie starts setting up her system outside as a warning for the kids.
At night, the two receive a radio transmission from a man named Rick, who says he is at a safe compound with plenty of supplies and food. He instructs them on how to make it to the compound down the river, telling them how dangerous it is to go down there with children, and how they will need to see in order to get through. Rick tells them to follow the sound of birds to find the place.
Tom wants to go to the compound, but Malorie thinks it could be a trap. Outside, the survivors from earlier make it to the house. Tom goes to confront them while Malorie and the kids get out safely. The survivors, led by "Whistling Marauder" (David Dastmalchian), order Tom to take off his blindfold. When they spot Malorie and the kids, Tom fires and kills three of the marauders before he takes one shot himself. Tom takes off his blindfold and kills two more before going after the leader, who is stalking Malorie and the kids. The entity starts to affect Tom, but he fights it long enough to kill the leader before turning the gun on himself, letting Malorie know Tom is gone. Malorie then gets the kids together to head onto the river.
It has now been 42 hours on the river, and they are fast approaching the rapids. They reach the bumpy waters, which Malorie tries to get through, but the boat flips over and everyone falls out. Malorie calls out to the kids and finds Boy in the water, while Girl has made it to the land, and Malorie finds her because Girl has a bell that she keeps ringing. The three then walk through the woods where the entity whispers to them and uses all its power to try and get them to see, but Malorie's will is stronger, and she gets the kids to listen to her and not look. She follows the sounds of the birds as they make it to the compound, but the entity surrounds them as she tries to make it inside until someone opens the door and lets them in.
Malorie's eyes are checked, and she and the kids are cleared for entry. They meet Rick (Pruitt Taylor Vince), and Malorie discovers that the compound is a school for the blind, and the people in there are protected from the entities. Malorie and the kids then find Dr. Lapham, who happily greets them. She asks the kids their names, and Malorie finally names them - Girl is named Olympia after her mother, and Boy is named after Tom. Malorie proudly says they are her children and she is their mother. Malorie then opens her bird box and frees the birds to be with the others in the sanctuary.