Lobo starts in Czarnia, a devastated planet. A rescue team searches for survivors among the debris, and find a baby. They're moved by that discovery, but, when the baby nearly tears one of the rescuers fingers apart with his mouth, he's left to die. His name? Lobo.
Years later, Lobo is an adult, skilled and mercyless bounty-hunter, caged by the Galatic Empire for his actions. One day, four dangerous alien criminals also captive by the Empire set free, and start looking for a mysterious object that can be used as a mass destruction weapon. Sided with Lobo, those four convicts are the most dangerous creatures of the Universe, and so, the Empire offers Lobo his freedon and his bounty-hunter license back if he manages to track down the convicts and, capture them and take them back in 24h.
Lobo's search leds him to Earth, in the small city of Indiana, where whe meet Kayla McGuee, a young and rebelious girl who posseses a strange necklace gave to her by her absent biological father. The necklace is the key for what the criminals are looking for: An artefact know as The Drown.
Both, Lobo and the criminals, find their way to Kayla's house, where a fight ensues. The villains escape, mistaking Kayla's adoptive father with the man they're looking for, as a hostage. Kayla tells Lobo about the Drown, and he tells her that it is a ancient artefact capable of giving telechinetical powers to it's owner. In case, Kayla's father, and, as such, she has mental habilities of her own. The duo unites to find the convicts before they use the necklace to track down Kayla's father and the Drown.