The 23-year-old, who has been named in the England squad for next month's Nations League games against Iceland and Denmark, has spent the last two seasons on loan at Sheffield United. His performances for Chris Wilder's team last season led to Henderson being linked with a summer move to Chelsea.
But Henderson has now committed his future to United, sparking the prospect of a battle for the No. 1 spot this season with David de Gea.
"The pathway that I have been on for the past five years has been fantastic for my development and the invaluable loan period at Sheffield United has been part of that," Henderson said. "The goalkeeping department at United is excellent; there are three top-level goalkeepers who have achieved so much in the game and I look forward to working with the group.
"The faith that the manager and the club have shown in me with this contract means a lot to me and will continue my progression as a goalkeeper.
"I'll be giving everything to improve every day so that I can play as many games as possible for this great club.
"Now I am looking forward to joining up with the England squad and then preparing for the season ahead."
United manager Ole Gunnar Solskjaer is now expected to keep Henderson in his squad for the coming season rather than loan him out again.
"We are delighted that Dean has signed his new contract," Solskjaer said. "He had another great season at Sheffield United, where he gained a lot of experience and grew both as a player and a person.
"Dean is a fantastic young keeper with the attitude and work-rate to keep improving every day.
"We are in a strong position within the goalkeeping department and that gives us the competition for places that we are looking for in the squad."