Deadpool kills Ajax after Ajax reveals he can't heal Deapool's disfigurations. Deadpool finally reveals himself to Vanessa, who looks past his disfigurement and embraces him as Colossus vows to make Deadpool an X-Man someday in the future.
Wade Wilson, aka Deadpool (Ryan Reynolds), is being driven wearing his full costume by cab-driver Dopinder (Karan Soni) and giving Dopinder ill-advised romantic advice. He gets out on the side of a bridge and jumps over, crashing into an SUV full of gun-men. A large fight breaks out between Deadpool and the convoy of mercenaries following the SUV. Deadpool demands they tell him where "Francis" is. He finally locates Francis and is about to apprehend him when he is interrupted by two members of the X-Men: super-strong metal-skinned Colossus and his young protégé Negasonic Teenage Warhead (Brianna Hildebrand). Their interference allows Francis to escape. Colossus asks Deadpool to join the X-Men, but he refuses and then escapes Colossus' clutches. Throughout, Deadpool breaks the fourth wall and tells us his origin story.
Wilson was an elite, extremely deadly special forces soldier who retired to work as a small-time mercenary. He lives a spartan lifestyle hanging out at the mercenary bar run by his good friend Weasel (T.J. Miller). He eventually meets a prostitute named Vanessa (Morena Baccarin) and the pair fall in love and begin living more wholesome lives. Wilson is soon thereafter diagnosed with untreatable cancer throughout his whole body. Though Vanessa begs him to stay with her, Wilson leaves while she is sleeping and enlists with a secret organization that promises to cure his cancer and give him super-powers if he will serve as a soldier for them.
Wilson is transported to a hidden facility run by maniacal doctor named Ajax (Ed Skrein) and his super-strong enforcer Angel Dust (Gina Carano). Ajax developed a method to activate latent mutant genes within humans using a form of intense torture and genetic manipulation. They then attach a control collar to the subject and force them to be hired assassins. Ajax himself has awoken his mutant genes, developing an inability to feel any pain. They eventually awaken Wilson's mutant genes, wherein he gains an incredible healing ability that heals his cancer. The process also leaves Wilson hideously disfigured, a condition that Ajax brags he can (but won't) cure. Wilson eventually learns that Ajax's real name is Francis and tries to escape and force Francis to heal his deformities. Francis stops Wilson from escaping (the facility is destroyed in the battle) and seemingly kills him, unaware that Wilson is now virtually immortal.
Wilson eventually recovers from his wounds and reconnects with Weasel. He also moves in with a blind old woman/drug dealer named Blind Al (Leslie Uggams). He is unable to approach Vanessa, concerned that she will be horrified by his disfigured body. Instead, Wilson devotes his life to tracking down Francis(which leads to the opening highway scene). Deadpool is despondent that he was unable to catch Francis and gain his cure. Deadpool learns that after the highway battle, Francis kidnapped Vanessa and is holding her hostage.
Dopinder drives Deadpool, Colossus and Negasonic to a meeting set by Ajax, Angel Dust, and some gun-men. A fight breaks out during which Negasonic and Colossus knock-out Angel Dust and, after giving them a chance to flee, Deadpool kills all the gunmen (except one named "Bob"). Deadpool and Ajax face off with Deadpool gaining the upper-hand. Ajax then reveals that nobody can cure Wade Wilson's deformities. Colossus gives Deadpool a heroic speech urging Wilson to rise above all that has been done to him and spare Francis' life. Deadpool gets bored during the speech and kills Ajax.
Colossus and Negasonic vow to make a still-reluctant Deadpool an X-Man before leaving (and Deadpool promises to try and be more heroic in the future). Vanessa approaches and takes off Deadpool's mask to reveal... that he has stapled a picture of Hugh Jackman's face to his own. She rips off this second mask and kisses him as the credits begin to roll.
In the post-credits scene, Deadpool explains the studio is out of money and can't provide a proper post-credit scene. He also announces that Cable will be in the sequel.
Thanks Evan B!