When Guy Ritchie calls “action” on the set of “The Man From U.N.C.L.E.” in early September, it will mark the end of a 35-year odyssey to tailor one of the most popular spy series of the 1960s into a major Hollywood movie.

Warner Bros. hopes to spawn a new franchise from the film, starring Henry Cavill and Armie Hammer as U.N.C.L.E. agents Napoleon Solo and Illya Kuryakin, respectively. Tom Cruise had been slotted for the lead role, but when he fell out in late May, the studio insisted its production budget be pared down to about $75 million before moving forward with the picture, targeted to be released next year. The movie, which one of the filmmakers describes as a fairly serious action pic set in the ’60s, will begin production Sept. 7, and film in London and Italy.

With a script by Ritchie and his “Sherlock Holmes” writer and producer Lionel Wigram, the film is an origin story that tells of the first pairing of the two spies — one American, one Russian. Unlike the friendly banter of the original series, the pair are initially hostile to each other, said someone familiar with the script. Ritchie declined multiple interview requests.

“The Man From U.N.C.L.E.” was, in its time, a pop-culture phenomenon. It was the first American TV series to tackle espionage themes in the wake of the James Bond films, and it made international stars of Robert Vaughn (Solo) and David McCallum (Kuryakin).

The secret headquarters of the United Network Command for Law and Enforcement — hidden behind a tailor shop in a block of Manhattan brownstones — and their high-tech gadgets were so clever that they inspired parodies from Mad magazine to movies (James Coburn worked for Z.O.W.I.E. in the “Our Man Flint” films).

The series’ success opened the door to a rush of intrigue, including such shows as “I Spy,” “Get Smart,” “Mission: Impossible” and “The Wild Wild West,” all of which were turned into feature films, with varying degrees of success.

Yet despite its remarkable pedigree (Ian Fleming was involved in the early stages and came up with Napoleon Solo’s name) and dedicated fan following, no one had been able to crack the code on a “Man From U.N.C.L.E.” movie made specifically for the bigscreen.

It’s not for want of trying.

“That’s been discussed for 40 years,” says Vaughn from his Ridgefield, Conn., home. As to why it’s taken so long, he says, “I’ve often wondered that myself.” In recent years, there has often been talk of casting Vaughn as the new head of U.N.C.L.E. (a role played in the series by Leo G. Carroll), although he says he has not been contacted about the part. (Between 1965-68, there were several smaller feature films that were cobbled together from TV episodes).

Producer John Davis (“Predator,” “Waterworld,” “Chronicle”) optioned “The Man From U.N.C.L.E.” in 1993, and has spent the past 20 years trying to get it off the ground. “I loved this as a kid,” he says. “It was the coolest show in the world. I had all the guns and the communication devices; I was just a fanatic. So when I came to Hollywood years later, I reached out to (series creator) Norman Felton, and set it up at Turner Broadcasting.”

He wasn’t the fi rst to try to get a studio to say “U.N.C.L.E.”

In 1977, Robert Short and Danny Biederman — fans of the show and novice filmmakers — spent five years trying to interest MGM (the primary rights owner) in a movie, to no avail. MGM even licensed the show to Viacom for a one-off TV-movie, “The Return of the Man From U.N.C.L.E.,” with both Vaughn and McCallum, in 1983.

Turner, which had inherited the rights to old MGM TV series, was acquired by Warner Bros., which is bankrolling the current production and will market and release the film around the world.

Since he started on his quest, Davis estimates he’s been through 12 or 14 different scripts, some of them from high-powered writers, including Jim and John Thomas (“Predator”), John Requa and Glenn Ficarra (“Bad Santa”) and Scott Z. Burns (“The Bourne Ultimatum”). Quentin Tarantino flirted with the project in the mid-1990s.

Directors who signed on at one time or another include Matthew Vaughn (“X-Men: First Class”), David Dobkin (“Wedding Crashers”) and Steven Soderbergh, who took the trouble to watch every first-season “U.N.C.L.E.” episode in preparation. Soderbergh got the closest to filming, even casting George Clooney as Solo at one point, but split with Warners over budget issues.

The casting of Solo, too, has been a merry-go-round over the past five years, with Bradley Cooper, Channing Tatum — and most recently, Cruise — all briefly onboard to play the American. The one constant throughout, Davis says, has been the Cold War setting: “The idea was that the best of all the world’s intelligence services were working to keep the world safe, with the most up-to-date technology that existed.”

So why has it taken so long for “U.N.C.L.E.” to be made?

“Everything has to align,” Davis says. “This is a filmmaker-driven project. Sometimes you have the right script and a new director will want to start over. It’s having that filmmaker, and that script that the filmmaker likes.”

Made From “U.N.C.L.E.”

“The Man From U.N.C.L.E.” was so popular in the mid-’60s that MGM cashed in with versions targeted for the bigscreen. But the films were simply footage from the shows viewers had seen at home, cobbled together with a bit of new material featuring more sex and more violence than was permissable on TV at the time.

The irst, “To Trap a Spy” (1965) was expanded from the show’s pilot, and made $2.1 million at the box office; “The Spy With My Face” (1965) was a spiced-up first-season episode, and collected $2.7 million at the B.O., the top earner among these adapted-for-bigscreen titles. “One Spy Too Many” (1966) was the first of the series’ two-parters. It minted $2.5 million theatrically.

All were released in the U.S. and, unlike the 1966 film based on the “Batman ” TV series for example (which shot an entirely new story for the bigscreen ), it was a cheesy way to fool fans. Ads billed the so-called movies “feature-length hits from the TV show.”

While the theatrical take may look small, the ilms’ costs were minuscule, and the titles were considered profitable.

Five more that originated as two-part episodes were released only in foreign markets: “One of Our Spies Is Missing” (1966); “The Spy in the Green Hat” (1967); “The Karate Killers” (1967); “The Helicopter Spies” (1968); and “How to Steal the World” (1968). They played frequently over the years on British TV, so much so that many U.K. fans remember the movies better than the series itself.

When stars Robert Vaughn and David McCallum reunited 15 years later, it was for a TV movie, “The Return of the Man From U.N.C.L.E.” on CBS in April 1983. It ranked among the week’s top 25 shows and, briefly, generated talk of a possible new series (or series of TV movies). Vaughn was interested, but McCallum was not, and “U.N.C.L.E.” has not been seen since.