The Love Actually star will have a supporting role in the spy film, according to The Hollywood Reporter.
Armie Hammer, Alicia Vikander and Man of Steel actor Henry Cavill will also feature in the adaptation of the TV series, which ran from 1964 to 1968.
Grant, who most recently starred in Cloud Atlas with Tom Hanks, will play the head of British Naval Intelligence.
The film follows special agents Napoleon Solo, played by Cavill, and Illya Kuryakin - Lone Ranger star Hammer - who work for the mysterious United Network Command for Law Enforcement (U.N.C.L.E.).
Swedish actress Vikander, known for her role as Kitty in Joe Wright's Anna Karenina, has been cast as the female lead, while The Great Gatsby's Elisabeth Debicki will also star in the adaptation.
Tom Cruise had been tipped for the role of Solo, originally portrayed by Robert Vaughn in the TV series, while George Clooney was set to play the lead role in director Steven Soderbergh's earlier version of the film.
However, Clooney withdrew from the film and Soderbergh subsequently dropped out of the project.
Director Ritchie will co-write the script with Lionel Wigram, who wrote both of Ritchie's Sherlock Holmes films, starring Robert Downey Jr.
Production is due to begin in September with a release planned for 2014.
There were 105 episodes of the multi-award winning TV show, The Man From U.N.C.L.E, with the first series broadcast in black-and-white.
Hugh Grant has been cast in Guy Ritchie's big-screen adaptation of the 1960s TV show, The Man From U.N.C.L.E.