Plot
In 1556, Don Aguirre leads Spanish conquistadors to South America to search for the Tears of the Moon, a mythical tree whose flowers can cure illness and lift curses, believing it may save his ill daughter. After many conquistadors die, the Puka Michuna tribe heals the survivors with the Tree's flowers. Aguirre asks for the arrowhead, that can reveal the Tree's location, but the tribal chief refuses, so Aguirre stabs him and burns the village. As his daughter escapes with the arrowhead, the dying chief curses the conquistadors, making them immortal and unable to leave sight of the Amazon River without being dragged back by the jungle itself.
In 1916 London, McGregor Houghton presents his sister Dr. Lily Houghton's research of the Tree to the Royal Society, which bars female members. The Houghtons hope to revolutionize medicine and aid the British war effort, so they request access to a recently acquired arrowhead that Lily believes can locate the Tree in Lágrimas de Cristal but are denied. Lily steals the arrowhead, narrowly evading Prince Joachim, who is equally intent on finding the Tree for himself and the German Empire.
After arriving in Brazil, Lily and MacGregor hire skipper Frank Wolff to guide them down the Amazon. Frank, who offers jungle cruises embellished with faked dangers, initially declines, citing the dangerous river and jungle, but reconsiders upon seeing the arrowhead. The trio departs after escaping Joachim's U-boat.
While snooping through Frank's cabin below deck, Lily discovers his research of the Tree, but he insists he stopped searching long ago. They are captured by cannibals that are actually the Puka Michuna who work for Frank as part of his contrived jungle cruise. Angered, Lily arrogantly accuses Frank of being a liar and decides to find the Tree herself. Tribal chief Trader Sam translates the symbols on the arrowhead, revealing the Tree's location at La Luna Rota, and that it only blooms under a blood moon.
Meanwhile, Joachim locates the conquistadors petrified inside a cave and partially revives them with Amazon water. Aguirre agrees to bring Joachim the arrowhead in exchange for lifting the curse when he finds the flowers. Joachim diverts river water to flood the cave which reanimates Aguirre and his conquistadors and infuses them with rainforest elements. The conquistadors attack the tribe and Aguirre stabs Frank through the heart. Lily flees with the arrowhead, chased by conquistadors, but the jungle vines pull them back to the river before they can catch her.
To the Houghtons' amazement, an alive Frank soon reappears and reveals he is also a cursed conquistador. He helped search for the Tree to save Aguirre's daughter but sided with the tribe against Aguirre's brutality. After years of endless fighting, Frank trapped his vengeful comrades in the cave away from the river, petrifying them. Failing to find the Tree, Frank remained tied to the river, becoming a tour guide and building a village; causing Lily to realise how wrong she was about him. Lily and Frank travel to La Luna Rota and discover a submerged temple containing the Tree. Meanwhile, Joachim has captured McGregor and forces him to reveal Lily's location. Frank, the Houghtons, the Germans, and the conquistadors all converge at the Tree.
Discovering the arrowhead is a locket containing a red gem, Lily inserts the two pieces into carvings in the bark; the Tree briefly blooms under the blood moon. As a fight ensues, Lily recovers one flower, while the German soldiers drown, Joachim is crushed by a falling rock, and Frank crashes his boat into the temple to block the river, petrifying himself and the rest of the conquistadors to save Lily. Realizing her true feelings for Frank, Lily sacrifices the flower to lift the curse and restore his mortality. The moon's last beam blooms a single flower, which Lily takes for research. Returning to the village port, Frank sells his business and leaves the Amazon to be with Lily.
Returning to Britain, Lily becomes a full professor at the University of Cambridge and sends McGregor on her behalf to reject an invitation to join the Royal Society. Lily and Frank then explore London together as she teaches him how to drive a car.
