Lobo is hired by Darkseid to kill Superman in retaliation for his ruthless execution of Kalibak. Lobo makes his way to Earth on his hog, tearing through the Watchtower on his arrival. Lobo goes to Metropolis, but is surprised to find the city completely destroyed. When Superman arrives, Lobo explains he was going to go on a destructive streak to get his attention but says, "Someone beat me to it."
Lobo then explains that Superman has a bounty on his head for his murder of Kalibak, which Lobo grins at and declares "Bad ass." When Superman asks if he's here to collect his bounty, Lobo tells him he's here to see if he's worth the trouble. After an intense staredown, Superman flies off, enraging Lobo who declares, "No one flies away from th' Main Man!" and he throws an entire building at Superman in retaliation.
Annoyed, the Man of Steel rises up unharmed and snatches Lobo by his jacket before flying them both into outer space and as close to the sun as possible. Superman drags a steaming Lobo back to Earth, explaining that while he can regenerate from a single drop of blood, there wouldn't be even that if he was tossed into the sun. Lobo decides Superman isn't worth the trouble for what "they're offerin'". After Superman studies him for a moment, he asks Lobo if he's one of the best manhunters in the galaxy.
Lobo responds, "No. I'm the best manhunter in the galaxy." Superman tells Lobo he has a job for him and tells him he wants him to hunt down Harley Quinn. Lobo agrees and tells Superman he needs something with her scent. Superman then leads Lobo to the Hall of Justice where Harley's old costume is on display. Lobo comments on this, saying, "You superheroes always keep th' crappiest trophies." Superman responds that he doesn't wanna know what kind of trophies Lobo keeps.
Lex Luthor approaches the two, questioning Superman about Lobo's presence. Annoyed by Lex's tone, Lobo grabs him by the neck and threatens him, though he backs down when Superman threatens to take him on another 'trip'. Lobo then notices the pill Lex is carrying and snatches it, demanding to know what it is. After Lex explains what the pill can do, Lobo decides he wants it as his payment for hunting Quinn. Though both Lex and Superman are unsure if the pill would even work on Lobo, the Main Man could care less, saying, "Maybe it does nothin'. Maybe I get to headbutt the moon in half."
Superman lets him keep the pill before asking him if he can get Harley's scent from her mask. Lobo agrees, explaining he can smell her insanity as well, though Lex finds this incredulous, but Lobo is quick to point out how nervous Lex smells. Superman then tells Lobo Harley was last seen in Gotham and tells him he wants her alive, with no collateral damage and no civilian deaths. Lobo growls, "You're takin' all th' fun outta this." before leaving for Gotham.
In Gotham, Lobo easily locates Harley in the sewers of the city, and is annoyed when she doesn't recognize him. She attempts to attack him with her hammer but the weapon smashes on contact with his head and he easily captures her. As he secures her hands, he compliments her for hiding in the sewers to escape Superman's senses but clarifies that, "No one hides from th' Main Man." and takes off on his hog with Harley on the back.
When he notices her moving around behind him and sees her wearing a fake mustache, he interrupts her before she explains and says, "No one should have ta justify th' greatness of a mustache." When Harley spots the super pill, she asks him what it is and Lobo fails to notices as he explains her freeing herself before snatching the pill and swallowing it.
Harley escapes and survives her fall with her new durability, annoying Lobo who catches up with her and sucker punches her. Angered, Harley throws him into an oncoming truck, consuming him in an explosion on impact. In between, Harley steals his hog and heads for Green Arrow's Arrow Cave for help. Lobo catches up soon enough, enraged further by her stealing his bike.
Before he can react, Green Arrow shoots off two arrows while ranting about how the Arrow Cave is supposed to be a secret location. Lobo scoffs, "Arrow Cave? What a stupid-" before screaming as the arrows hit him in the eyes, blinding him. Black Canary then brings him to his knees with her canary cry, allowing Harley to rip his head off.
In-between, she reattaches his head and binds him down securely, with Lobo dreaming of fighting multiple versions of himself and being overwhelmed. When he awakens, he is horrified when Harley tells him, "It's time to talk about your feelings" and screams "NOOOOOOOOOOOOOOOO!"
Harley manages to easily figure out that Superman emasculated him earlier and that he feels he no longer has power. Lobo insists he is "Plenty masculated" but when Harley points out that he's wasting time hunting her, he agrees, saying, "Crap. Yer right. Yer way beneath me." He then asks what he's supposed to do and when Harley tells him he needs to take his power back, Lobo grins and says, "I get it. Yer sayin' I need to frag somethin' worth fraggin'!" Lobo then easily escapes his bonds and hops on his hob, telling Harley they're done before leaving.
Sometime later, he goes to Apokolips and challenges Darkseid to a battle by putting a lit cigar out on the dread lord's head.
Lobo is hired by Metron to kidnap Blue Beetle due to the looming battle between the Red and Green Lanterns as Starro has been brought in by the side of the former. Once Blue Beetle is taken to Metron, Lobo is given the new task of protecting the scarab's new carrier alongside the rest of the Teen Titans.
In their first engagement against the Red Lanterns, Lobo fights Atrocitus, but his lower torso is sliced off by Atrocitus. Heavily outnumbered, the Titans bring Lobo with them to Oa to think of a new plan. As his spacehog is lost in space with his lower body, Lobo is given a new power ring to join the others. Aiming straight for Atrocitus, Lobo proceeds to first kick Dex Starr off the fight with a willpowered boot. After which, he conjures up a penis created from willpower to attack Atrocitus.