A mysterious black-clad gunfighter wanders a mystical Western landscape encountering multiple bizarre characters.
El Topo decides to confront warrior masters on a transformative desert journey. He begins with his six-year-old son, who must bury his childhood totems to become a man. El Topo (the mole) claims to be God while dressed as a gunslinger in black, riding a horse through a mystical landscape strewn with American Western and ancient Eastern religious symbols. Bandits slaughtered a village on his path, so El Topo avenges the massacred, then forcibly takes their leader's woman Mara as his. El Topo's surreal way is bloody, sexual, and self-reflective, musing of his own demons, as he tries to vanquish those he encounters.—David Stevens
El Topo, carrying a black umbrella, travels through a desert on horseback with his young son, Hijo, who wears nothing but a hat and a pair of moccasins. They stop near a pole and El Topo hands Hijo a teddy bear and a hand mirror with a picture of his mother. El Topo tells Hijo that he is now 7 years old meaning that he is now a man and to bury his first toy and his mother's portrait in the sand. Hijo buries the picture and the teddy bear the portrait while El Topo plays his flute. They later come across a town whose inhabitants have been slaughtered, and El Topo hunts down the perpetrators. El Topo and Hijo are traveling, when they are stopped by 3 bandits who El Topo kills, except for one who he chases and shoots multiple times with a rifle, until the bandit tells him that it was the Colonel, along with 5 other men, and that they are at the Franciscan mission. One of the bandits in the cathedral town murders several of the townspeople, while the other 4 do homosexual activities with the monks. El Topo arrives kills two of the bandits, castrates the Colonel (who then commits suicide), and the townspeople kill the remaining 3 bandits. El Topo abandons his son to the monks of the settlement's mission and rides off with the woman whom the Colonel had kept as a slave. El Topo names the woman Mara, and she convinces him to defeat four great gun masters to become the greatest gunman in the land. Each gun master represents a particular religion or philosophy, and El Topo learns from each of them before instigating a duel. El Topo is victorious each time, not through superior skill but through trickery or luck.
After the first duel, a black-clad woman with a male voice finds the couple and guides them to the remaining gun masters. As he kills each master, El Topo has increasing doubts about his mission, but Mara persuades him to continue. Having killed all four, El Topo is ridden with guilt, destroys his own gun and revisits the places where he killed those masters, finding the first master's grave covered with honeycombs and swarming with bees, the second master's grave covered in a pyramid of sticks, and the third master's grave on fire. The unnamed woman confronts El Topo and shoots him multiple times in the manner of stigmata. Mara then betrays him and rides off with the woman, while El Topo collapses and is carried away by a group of dwarfs and mutants.
El Topo awakens in a cave to find that the tribe of deformed outcasts have taken care of him and come to regard him as a God-like figure while he has been asleep and meditating on the gun masters' "four lessons". The outcasts dwell in a system of caves which have been blocked in - the only exit is out of their reach due to their deformities. When El Topo awakens, he is "born again" and decides to help the outcasts escape. He is able to reach the exit and, together with a dwarf woman who becomes his lover, performs for the depraved cultists of the neighboring town to raise money for dynamite to assist in digging a tunnel on one side of the mountain where the outcasts have effectively been kept imprisoned.
Hijo, now a young monk, arrives in the town to be the new priest, but is disgusted by the perverted form of religion the cultists practice. El Topo goes to the church and unknowingly asks Hijo to marry him and the dwarf woman, Hijo becomes happy that there are still people in love. However, Hijo recognizes him and threatens to kill him on the spot for abandoning him as a child, but agrees to wait until he has succeeded in freeing the outcasts. Hijo grows impatient at the time the project is taking, and begins to work alongside El Topo to hasten the moment when he will kill him. At the point when Hijo is ready to give up on finishing the tunnel, El Topo breaks through into the cave. The tunnel has been completed, but Hijo finds that he cannot bring himself to kill his father.
The outcasts come streaming out, but as they enter the town, they are shot down by the cultists. El Topo helplessly witnesses his community being slaughtered and is shot himself. Ignoring his own wounds, he massacres the cultists, then takes an oil lamp and immolates himself. His girlfriend gives birth at the same time as his death, and she and his son make a grave for his remains. Hijo and the dwarf woman with the baby ride off on horseback, the son now wearing his father's black gunfighter clothes. El Topo's grave is shown covered with honeycombs and swarming with bees, just like the first gun master's grave.