Deadpool was hired by Dr. Francis Talbot to travel back through time in order to save his grandson from dying in the Gulf War. Once Deadpool made the jump, he decided to use the time travel device to change historical points in Earth's past instead.
He went back to Germantown during 1777, but his plans got interrupted when Cable and his X-Force team showed up after being hired by Talbot to keep Deadpool from changing key moments in history. Deadpool became distracted by Cable after he tried to talk to him, but this was only a ploy so X-Force could move in and take the mercenary out.
This caused him to get trapped in the mansion's basement but Deadpool escaped once again through the time-stream to Gettysburg in 1862. Now in 1862, Deadpool allied himself with a battalion of soldiers from the Confederate Army. The changes he made back in Germantown had affected the timeline allowing the soldiers to have tanks and robots during the American Civil War. This gave Deadpool a huge advantage over Cable and his group after they showed. Deadpool and his soldiers kept the mutants, Warpath and Domino at bay with the advanced technology while Cable traveled back to 1777 to check on the others.
As Deadpool lost his list of things to change, Cable reappeared prompting a fight between the two of them. Wade began to teleport with Cable in tow to the year 1900. Once they materialized, Deadpool slapped a inhibitor collar on Cable to suppress his powers. Here Deadpool revealed Talbot's reasons for why he sent Cable back in time, so that he would be killed, and that Deadpool could change history at pivotal moments, turning America into a bloodthirsty, war-mongering super-power. The both of them fight some more, with Cable eventually blowing Deadpool up. But his healing factor kicked in and repaired his body. After a huge battle against some Chinese soldiers, Deadpool reclaimed a secondary prototype time-machine from the Empress and traveled to 1923 Germany to confront Adolf Hitler.
Deadpool spends the next 23 years protecting Adolf Hitler in the past, including killing any other time travelers who appear with the intention of killing him which alters the timeline again. Talbot was able to send a message back to 1944 instructing Deadpool to travel to the present with Hitler, where he confronts the heroes in an attempt to kill them. A battle ensues, with X-Force taking on the Panzer-Sentinels while Cable confronts Deadpool. Deadpool takes him out and then prepares to finish Cable off by firing a blast from his Time Gun Machine but Cable uses his telekinesis to deflect the attack and instead, sends the energy at Talbot killing him, allowing the timeline to reset back to normal.