A native of Hollywood, California, MacDuff was the son of Tyler Duff, Sr. (1890–1967), originally from Indiana. His mother was Cecil W. Duff (1893–1978), an Illinois native. In 1943, at the age of eighteen, MacDuff joined the U.S. Navy. In 1944, he drove an LCVP landing craft in the first wave of the invasions of Saipan and Guam. In late 1944 and 1945, he was part of General Douglas MacArthur's invasion forces in the Philippine Islands.
MacDuff played Emmett Dalton in the 1957 episode "The End of the Dalton Gang (October 5, 1892)" on the CBS documentary series, You Are There. He appeared that same year in the first season of ABC's Maverick as Drake in "Relic of Fort Tejon". He played Bill Corey in "Lost River Roundup" of the series Sergeant Preston of the Yukon. In 1958, he was Townsend in "The Gallant Foe" of the American Civil War drama Gray Ghost, based on the exploits of the Confederate Major John Singleton Mosby. In 1957–1958, MacDuff appeared twice on Dale Robertson's first and most successful western series, Tales of Wells Fargo. In 1960, he portrayed Reggie Lemaire in the episode "Mystery at Malibu" on Ronald W. Reagan’s CBS anthology series, General Electric Theater. Other MacDuff guest-starring role were as Ira Burns in the episode "Get Dawson" of the 1960 police drama This Man Dawson starring Keith Andes, Alcoa Theatre, Lawman, Lassie, and James Arness's Gunsmoke.
In 1952, MacDuff in one of his first uncredited roles appeared as a Cheerleader in the film Bonzo Goes to College. From 1953–1957, he appeared three times as Brad Stanton, Clint Harkey, and Kip Holloway on the series The Lone Ranger. He was the only person on the program to say both "Who was that masked man?" and "That was the Lone Ranger!"
In 1954, he appeared on CBS's Schlitz Playhouse in the episode entitled "At the Natchez Inn". That same year, he guest starred on Jim Davis's syndicated Stories of the Century in the role of Bob Ford, the Assassin of Jesse James in the episode "Frank and Jesse James". In 1954, he portrayed Billy the Kid in the film, The Boy from Oklahoma, with Will Rogers, Jr., as Tom Brewster. The film is the basis for the 1957–1961 television western Sugarfoot, starring Will Hutchins as a tenderfoot studying to be a Lawyer. That same year, MacDuff played Frankie in the episode "The Boy Who Hated Superman" on the George Reeves series, Adventures of Superman. In 1955, he portrayed a delivery man in the "Olsen's Millions" episode of Superman.
In 1956, MacDuff appeared in the syndicated anthology series Death Valley Days in the role of Norman Berry in the episode "The Hoodoo Mine". That same year, he appeared four times in different roles on the Gail Davis series, Annie Oakley. He was the title guest star in the episode "The Saga of Clement O'Toole", the story of a young Philadelphia grocery store clerk who comes to Arizona to start a new life but who is mistaken by townspeople for a Kansas outlaw, who had previously used the alias "Clement O'Toole". That same year, he appeared as Stacy in the episode "Christmas Present" in the series The West Point Story.
In 1957 and again in 1967, he was the dialog Director for Raymond Burr's two series, Perry Mason on CBS and Ironside on NBC. He also appeared in two Perry Mason episodes in 1958 and 1965. In "The Case of the Lucky Loser", based on a 1957 Erle Stanley Gardner novel, MacDuff, in the role of Theodore Balfour, is charged with the murder of his uncle, played by Bruce Bennett. The trial ends in a hung jury, and Theodore's attorney advises him to accept a plea bargain of involuntary manslaughter. Having believed that his grandson's Lawyer erred, the grandfather, Addison, played by Richard Hale, retains Perry Mason to reopen the case, clear Theodore's name, and find the real killer, who turned out to be the victim's wife, played by Patricia Medina. In 1993, in one of his last acting roles, MacDuff played the part of W.J. Cronkite in Perry Mason: The Case of the Skin-Deep Scandal, a television movie.
