After a scientist is mysteriously killed while assisting a top-secret bioengineering project in the swamps of the American South, government worker Alice Cable arrives at the bogs to serve as his replacement. Alice immediately notices that one of the team's swamp sensors has malfunctioned, but her guide, Charlie, introduces her to Harry Ritter, the project supervisor. Charlie tells Ritter a rumor about an evil paramilitary leader named Anton Arcane, who intends to hijack their operation. While Charlie briefs Ritter on the situation, Alice introduces herself to Dr. Linda Holland and her brother, lead scientist Dr. Alec Holland, who takes her on a tour and encourages her to admire the beauty of the swamps.
Upon returning to the site, however, Ritter and Charlie scold Alice for distracting Alec. When Alice mentions the broken sensor, Ritter reveals that her predecessor was attempting to repair it when he was killed. After noting the disappearance of one of their workers, the group hears a loud bang and returns to the laboratory, where Linda shows off her recent breakthrough: a glowing, plant-based concoction with explosive properties. Alec then shows Alice a hybrid plant and animal cell, his prized discovery. Sometime later, Alec notices that droplets of Linda's formula spawned rapid plant growth on the surfaces they touched. Overcome with excitement, Alec kisses Alice before sending her to retrieve Ritter in the control room. Although the room is empty, she sees security camera footage of Charlie being shot. Suddenly, a group of paramilitary agents attack her and raid Alec's laboratory. A man resembling Ritter steps forward, but pulls off his mask and reveals himself as Arcane. When Arcane shoots Linda for attempting to escape with the formula, Alec grabs the beaker, but trips, causing the spilled chemicals to set him on fire. He runs outside and dives into the swamp to extinguish the flames as a series of explosions burst from the water.
Overnight, Arcane's henchmen destroy the premises and remove all evidence of the team's work. At dawn, a henchman captures Alice and attempts to drown her in the swamp, but a green, humanlike creature drags her ashore and chases two of Arcane's men. Meanwhile, in his mansion, Arcane and his secretary realize that Alec's most recent notebook is missing from the plunder. Alice runs to a nearby gas station to telephone her employers for help; the operator connects to Ritter, who claims to have been called away from the site before the attack. After revealing she stole Alec's last notebook, Alice waits for Ritter's return alongside the young gas station attendant, Jude, but Arcane's men arrive and chase her through the forest. Suddenly, the Swamp Thing appears and again scares the pursuers away, immune to their gunfire. Once alone, Alice attempts to escape the monster, and it reluctantly trudges back into the trees. Jude finds Alice and leads her to a nearby cabin to change clothes. Later, Arcane instructs his men to find Alice, hoping she will lead them to the creature.
Alice and Jude boat around the swamp until they reach the dock near the laboratory wreckage. She spies the Swamp Thing crouched among the ruins, holding Linda's locket, and quickly returns to the boat, vowing to bring Alec's final notebook to Washington, D.C. Minutes later, multiple boats of Arcane's men close in on Alice and Jude, luring the creature from its hiding place among the reeds. Despite their bullets and grenades, the Swamp Thing engineers an elaborate boat crash. Although concerned by its intelligence, Arcane orders his lead henchman, Bruno, to continue the search. Moments after instructing Jude to escape with Alec's notebook, Alice hears the boy cry out in distress, but she is kidnapped before she can reply. The Swamp Thing finds Jude's lifeless body and presses a hand against his head, creating a greenish glow which instantly revives him. Regaining consciousness, Jude realizes the creature is a friend of Alice's and gives it the notebook for safekeeping. On Arcane's boat, Alice throws her kidnapper, Ferret, overboard, then dives into the water and swims ashore. Once on land, Alice bumps into the Swamp Thing, which calls out her name. Ferret chops off the Swamp Thing's arm with a machete, but the creature easily snaps Ferret's neck, causing Alice to faint. She awakens in the monster's embrace as it presents her with an orchid plant. The Swamp Thing speaks to her, and she recognizes it as Alec. Later, she strips naked and goes skinny dipping in the water as the monster paces along the banks. After Alice dresses, Arcane's men follow her, capture the Swamp Thing in a net, and retrieve the final notebook.
That evening, Arcane invites Alice to a formal dinner party celebrating his duplication of the Hollands’ formula. Moments after giving a toast to prospective immortality, Arcane reveals that he secretly slipped the first dose to Bruno, who begins to convulse. The hulking man's body shrinks to half its size as he grows pointed ears and a misshapen skull. Arcane locks him in a dungeon alongside the Swamp Thing, asking the latter creature why the experiment failed. The Swamp Thing reveals that the formula does not produce strength, but instead amplifies a person's natural qualities, explaining that Bruno's timidity caused his diminished stature.
After locking Alice in the dungeon with them, Arcane returns to his study and drinks a glass of the formula. A beam of sunlight emitted through the door re-grows the Swamp Thing's missing arm, allowing the creature to free itself, Alice, and Bruno. Upstairs, Arcane transforms into a hairy, boar like beast, and descends to the dungeons. There, he discovers that his captives have escaped through an underwater tunnel leading back to the swamp. Sometime later, Alice and the Swamp Thing emerge from the water, followed closely by Arcane's monster, which stabs Alice with a sword. The Swamp Thing revives Alice who alerts him to Arcane, whom he ultimately kills. The creature turns to leave, but Alice pleads for him to stay so that she can help him rebuild his work. He refuses, but promises to return to her soon. Moments later, Jude emerges from the trees and embraces her as they watch the Swamp Thing lumber away through the marsh.
