A prelude tells the beginning of the Book of Genesis. In the beginning, there was nothing. Then God created the world as well as man and woman. After Adam and Eve created sin, they had three sons - Cain, Abel, and Seth. After Cain killed Abel, he took refuge under the eyes of fallen angels called the Watchers, giant multi-armed stone golems. The Watchers helped Cain and his descendants build an industrialized civilization, but the wickedness of man spread throughout the world. Only the descendants of Seth would be left to restore mankind.
The story begins with Noah shown as a young boy, standing on a hill with his father Lamech . Lamech is about to give him a precious heirloom - the skin of the original serpent from Eden, which has been passed down for many generations. Suddenly, a large crowd approaches, led by a young king named Tubal-Cain (Ray Winstone), who wants to make that hill into a mine. Seeing Lamech, Tubal-Cain kills him and takes the serpent's skin, while Noah runs.
Many years pass. The adult Noah (now played by Russell Crowe) is living with his wife Naameh (Jennifer Connelly) and his three sons, Shem (Douglas Booth), Ham (Logan Lerman), and Japheth, when he sees a small miracle: a drop of water hits the ground and a flower grows instantly. That night he has a dream where he sees the mountain his grandfather Methuselah lives on, and water covering the Earth. He realizes that the Creator is trying to send him a message. He and his family journey to see Methuselah and seek guidance. Along the way, they find a group of recently killed humans, and among them, a girl that is wounded but still alive, named Ila (Emma Watson), and they adopt her. Some of Tubal-Cain's men find then chase Noah and his family, but cease pursuit as they are afraid to enter a dark region inhabited by the Watchers.
It is recounted that the Watchers are friends of Methuselah (Anthony Hopkins) because he had once defended and saved them. They came to Earth to help the humans, but after learning from them, the humans tried to enslave and kill them. Attempting to flee, Methuselah aided their escape by fighting waves of human soldiers with a burning sword wielding tremendous power. One of them, Magog (Mark Margolis) rescues Noah and his family from the other Watchers, who distrust all humanity, telling Noah that he senses that Noah is a good man, like his father.
Noah speaks with Methuselah and receives a seed passed down from the Garden of Eden. He plants the seed on a plain, and a great spring erupts from the earth - extending out as a great network of streams in all directions - and an entire forest grows around its source within moments. The miracle convinces the Watchers that Noah is chosen by the creator. Noah asks for their aid in the building of an ark, and they agree to help in the undertaking.
Roughly eight years pass. As the Ark nears completion, animals are seen following the streams from across the land to the source of the great spring and begin arriving to the ark. They enter and settle into the ark and are put into a deep sleep by incense that Noah and his family prepare and dispense throughout the mighty vessel. Meanwhile, the surrounding lands have been running short on food sources and the humans, led by Tubal-Cain, are becoming exceedingly ravenous for flesh. A horde of about 200 men, led by self-declared king Tubal-Cain, approaches the Ark and threatens to storm it, but the Watchers force him to turn back.
Noah realizes that his three sons need wives, and that Ila cannot serve because she is barren. He disguises himself and goes into the human camp in order to find three women, and take them into the ark. At the human camp, he sees humans being traded and apparently slaughtered for food, living in feral, crowded and filthy conditions. Stunned by the wickedness of Tubal-Cain's followers, Noah gives up the effort, becoming convinced that the Creator wishes for the entire human race to come to an end. Later in the forest near the camp, Methuselah blesses Ila and her barrenness is cured.
Shortly before the rains start to pour, Ham decides to go to the camp himself and find a woman. He falls into a pit filled with the dead and encounters a frightened young girl named Na'el. She is willing to go with him, but as they run back to the ark, her foot gets caught in an animal trap. Noah comes to help but sees the human horde coming to raid the ark, so he forces Ham to leave her behind and save himself. Seconds later, the human horde reaches her and tramples her to death as it passes. All of Noah's family boards the ark except Methuselah, who chooses to die in the flood. As the ark is launched, all the Watchers sacrifice themselves fighting the endless human waves. As they die, they return to their original forms and are spirited skyward as their Creator forgives them. As the flood waters pour toward the ark and his remaining soldiers drown, a wounded Tubal-Cain seizes the opportunity to survive and crawls up a pathway to a high point of the ark, hacking his way inside the vessel where he is eventually found by Ham. The wicked old king plays on Ham's anger toward Noah for allowing Na'el to die. Outside, the family listens to the dying screams of those outside the ark. His family implores him to let some of them in, as they "have room," only for a weary Noah to reply that there is no room for them - that their fate was sealed.
Ila wakes up, feeling ill, and goes to Naameh who deduces that she is with child. At this exact moment, the rains stop completely. Ila says it is because the Creator smiles upon the unborn child. Naameh, Shem, and Ila inform Noah of Ila's good fortune, but the patriarch rationalizes that the Creator's wish to destroy humanity also extends to his own family, who he initially thought would simply die of old age once the flood waters recede. He tells the family that if the child is a boy then he will replace their youngest as the last man, but if a girl is born, he will kill the child upon her birth, much to Ila's horror - believing this to be a test for him by the Creator of his faith and resolve to carry out the undertaking to completion. Not truly willing to do such a thing so much as feeling it is a duty to the Creator, a tearful Noah climbs to the top of the ark and asks for the Creator's counsel. Finding no answer, Noah resolves to do as he told his family. Meanwhile, Tubal-Cain finds aid from the naive Ham (eventually acquiring the boy's help in a plot to kill Noah) and Naameh makes one final, unsuccessful attempt to dissuade her husband.
Many months pass. Ila, now near the end of her pregnancy, and Shem build a small raft to escape Noah's plot to kill their child. Noah discovers their plan and burns the raft. The shock causes Ila to go into labor. With Naameh's assistance, the terrified young girl gives birth to twin girls. Hearing the babes' cries, Noah pursues Ila to the top of the vessel. As Ila pleads for a moment to sing to the crying infants to pacify them before they die, Noah hears the song he once sang to Ila when young and frightened - then looks upon the girls and decides not to carry out the unspeakable task.
Tubal-Cain has seemingly manipulated Ham into believing killing Noah is just and will be for the sake of Ila and Shem's offspring as well as vengeance for Na'el, so Ham lures Noah to the tail end of the ark on the pretense that the animals have awoken and have begun cannibalizing each other. As Noah and Tubal-Cain engage in a brutal fight, the Ark hits a mountain and Tubal-Cain is thrown through the shattered wall of the vessel, being greatly injured. As the king rises and attempts to finish off a similarly-injured Noah, a repentant Ham stabs Tubal-Cain in the ribcage, killing him.
As the rest of the family begins making a new life for themselves on newly discovered land as the flood recedes, Ham decides it is time for him to leave, still angry at Noah for what happened to Na'el. Noah, believing he'd failed God, imbibes of wine and becomes a drunkard, living in a cave separate from his family. One day Ham finds his father lying naked and unconscious. He walks away, leaving Shem and Japheth to cover their father with a blanket. Ila confronts Noah on allowing his grandchildren to survive, telling him that perhaps it was the intent of the Creator to give him the choice of whether mankind should be saved or not. When she asks why he didn't kill the babies, Noah reveals he could feel nothing but love for the babies upon seeing them - allowing him to see the goodness in mankind. Noah decides to rejoin his family. He and Naameh reconcile in her garden and she forgives him.
Later, the family stands atop a cliff face and Noah blesses them all as the beginning of a new human race. They watch as the Creator sends a rainbow from the sky, covering all of the Earth, signaling his promise to never destroy mankind again.