El Topo, a figure shrouded in mystery, journeys through a vast desert while evoking poignant emotions as he rides alongside his young son, Hijo, who is barely dressed apart from a hat and a pair of moccasins. Their trek brings them to a lone pole where El Topo presents Hijo with a teddy bear and a hand mirror that holds a picture of his mother. In a moment of profound meaning, El Topo explains to Hijo that he has now reached the age of seven and is thus a man, urging him to bury his cherished toys—his mother's portrait and the teddy bear—beneath the sands. As Hijo buries his first cherished belongings, El Topo enchants the atmosphere with his flute melodies.
However, their journey soon takes a dark turn as they stumble upon a town that has been mercilessly ravaged. Consumed with rage, El Topo sets out on a vengeful quest to hunt down those responsible for the massacre. On their travels, they encounter three bandits who threaten them; El Topo skillfully deals with them, leaving only one alive. Through a tense confrontation, the surviving bandit reveals that a Colonel, with five others, has orchestrated the chaos and is residing at the nearby Franciscan mission.
The situation escalates when one of the bandits, now hidden in the cathedral town, gruesomely slaughters several townsfolk, while the others engage in illicit activities with the monks. El Topo arrives, delivering deadly justice by slaying two bandits and castrating the Colonel, which drives the tyrant to take his own life. In the aftermath, the townspeople rise and eliminate the remaining three bandits. Following this bloody encounter, El Topo makes a heart-wrenching decision to leave his son with the monks and departs with a woman named Mara, who had previously been enslaved by the Colonel.
Mara, a compelling character, inspires El Topo to confront and defeat four legendary gun masters in his pursuit to become the most renowned gunman in the land. Each master's philosophy or religion provides El Topo with vital lessons as he challenges them. Surprisingly, El Topo prevails not through sheer skill, but rather through cunning and sheer luck.
After securing his first victory, a mysterious black-clad woman finds them and guides El Topo to the remaining masters. As his wins accumulate, so too does El Topo's inner turmoil, yet Mara's manipulation keeps the fire of ambition alive within him. Ultimately, having triumphed over all four masters, he becomes engulfed in guilt and remorse, which leads him on a poignant pilgrimage to the sites of his violent encounters. He discovers that the first master’s grave is adorned with honeycombs and buzzing bees, the second covered with a neat stack of sticks, and the third engulfed in flames.
The unnamed woman confronts El Topo yet again, inflicting wounds reminiscent of the stigmata. In a devastating twist, Mara betrays him, riding off with the mysterious woman, leaving El Topo to collapse, only to be carried away by a group of deformed outcasts.
Upon awakening in a cave, El Topo learns that these outcasts, who see him as a God-like figure during his slumber, have been fervently caring for him. Realizing their state—trapped in caves with no means of escape due to their deformities—El Topo is reborn with a newfound purpose. Determined to aid them, he strives to reach an exit while forming a romantic relationship with a dwarf woman among the outcasts. To support their escape, he performs for the local depraved cultists to raise money for dynamite.
Meanwhile, Hijo matures into a young monk and arrives in the same town expecting to serve as its new priest. However, he is immediately disheartened by the corrupted version of religion practiced by the cultists. In a surprising twist of fate, El Topo unknowingly approaches Hijo with a proposal to marry him to the dwarf woman, inadvertently bringing joy to Hijo, who relishes that love still exists. Yet, once the recognition dawns, Hijo feels a surge of rage and contemplates vengeance on the man who abandoned him, choosing instead to wait until the outcasts are freed.
As the project to excavate a tunnel progresses, impatience grips Hijo, leading him to join El Topo in hastening the monumental task. Just as Hijo is about to give up hope, El Topo breaks through, unearthing the path to freedom. However, when the outcasts pour into the town, they are met with a vicious hail of gunfire from the cultists, tragically threatening all that he has fought for.
In a desperate act of defiance, El Topo witnesses the slaughter of his newfound community, ultimately succumbing to his own wounds. Ignoring his agony, he exacts vengeance by taking down the cultists and, in a final act of self-sacrifice, ignites an oil lamp, leading to his own immolation. As this tragedy unfolds, his beloved gives birth simultaneously, and together with Hijo, they lay him to rest, creating a grave adorned with the same honeycombs as the first gun master’s final resting place. The image of Hijo riding away with his newborn sibling in his father's iconic black gunfighter attire echoes the legacy of El Topo, embedded forever in the sands of time.
