Hired by A.I.M. to locate the zombified, disembodied head of Deadpool from Earth-2149 (later Headpool), Deadpool-616 had a change of heart and decided to help Headpool return to his own dimension. Deadpool, Headpool and Doctor Betty Swanson (an A.I.M. scientist and Deadpool-616's contact within the organization), and A.I.M. agent Bill traveled to the Florida Everglades so that Deadpool-616 could use the Nexus of all Realities, a local point that unities all dimensions, to return Headpool home to his dimension. However, two dimensional counterparts entering the Nexus at the same time caused a disruption in the Nexus, sending Deadpool and Headpool to various other dimensions, locking to the location of that reality's Deadpool. The pair first traveled to Earth-6466 where they met Major Wilson, code name Deadpool of SHIELD, who captured them believing that they were scouts sent from an evading force through the dimensional portal. Tricking Major into believing Headpool was a symbiote and the pair needed each other to survive, Deadpool-616 gained the upper hand and escaped with Headpool into the dimensional portal.
The duo then traveled to Earth-3010, where the USA removed all alienable rights and liberties of its people, creating a fascist state enforced by that realities Captain America (later General America), SHIELD, and the giant robotic Sentinels. While there, they encountered Lady Deadpool, who was battling General America. The Deadpool duo helped Lady Deadpool escape capture, when Deadpool-616 hurled Headpool at General America, allowing him to bite the arm of the other-world hero. Deadpool-616 severed the arm from General Americas body to stop the spread of the zombie virus. After a quick goodbye the duo entered the dimensional portal again taking the infected arm with them. The duo next traveled to Earth-1108 where Deadpool-616 swiftly shot and apparently killed the cowboy Deadpool Kid. After they returned to Earth-616, Sorcerer Supreme Doctor Voodoo stabilized the Nexus to allow Deadpool to return Headpool to his home dimension. Deadpool and Headpool entered the portal, but once the Man-Thing (Ted Sallis), guardian of the Nexus, appeared Dr. Swanson and Bill entered the portal as well to escape Man-Thing.
Later on, Deadpool-616 was contacted by the Elder of the Universe known as the Contemplator to recruit a team of alternate dimension versions of himself to save the Multiverse. Having already come into contact with alternate versions of himself and generally getting along with "himself," Deadpool readily agreed. He first returned to Earth-3010 to recruit Lady Deadpool, who he once again help to escape General America. He next traveled to Earth-10330, an Earth where Xavier institute became a boarding school for mutant boys like Cyclops, Wolverine, Colossus, Angel, and others, where he recruited Kid Deadpool, who believed that he was destined for bigger and better things, surpassing the other students ambitions. Deadpool finally traveled to Earth-103173, a reality where scientist Von Braun and Eigor conducted the Mascara-X Project, a process similar to Earth 616's Weapon X Program, on a dog in hopes to create a new process for Babelline Cosmetics company that would give its customers eternal youth. Believed dead, the scientist discarded the dog's body, but it was discovered by a local circus who exploited the dog's power giving the name "Deadpool, the Daredevil Dog" until Deadpool recruited him for the Deadpool Corps.
After the successful completion of their first mission, to defeat the universal threat known as the Awareness, the Deadpool Corps was approached by the Omega Confederation of Planets to stop the pirate known as the Blue Buccaneer from wreaking havoc throughout their territories. Upon the Corps engagement of the Blue Buccaneer it was revealed that he was the Elder of the Universe known as “The Champion.” (The Corps had prior dealings with Champion due to his disagreement with fellow Elders Contemplator and the Grandmaster who felt that the Corps were the perfect candidates to defeat the Awareness. The Champion set out to test the Corps’ worthiness. He was swiftly defeated by their unorthodox methods and savage cunning.) The Corps once again outsmarted the Champion and he was left floating in the wreckage of his ship.
Pleased with Corps’ results the Omega Confederation gave them another assignment, to squash the rebellion of the indigenous Krook on the resource-rich planet of Kagan 7. This mission led to the Corps having a division amongst its members, as Lady Deadpool, Dogpool and Headpool allied with the Krook King, while Deadpool and Kidpool took up allegiances with his daughter Princess Teela, who was in favor of the modernization of the planet. Kidpool contracted the Deadpool former love interest, intergalactic smuggler/arms dealer Broken Blade to upgrade the Krooks’ primitive weapons and train their troops in the use of the modern weapons. Realizing that there was more to Teela and Deadpool’s association than the business at hand, Broken left before completing the training of the troops.