Nelson was born in New Orleans, Louisiana. He began acting while attending Tulane University in New Orleans. He left college after two years to study at the New York School of Radio and Television Technique. He served a tour of duty with the United States Navy as a radioman on the light cruiser USS Dayton. He took a position as a director at WDSU-TV in New Orleans. By 1956, acting became his central focus, and he moved to the Los Angeles area.  Early in his career he worked with famed B-movie producer Roger Corman on the films such as The Cry Baby Killer, A Bucket of Blood, Teenage Cave Man, and Attack of the Crab Monsters. In 1958 he participated in Bruno VeSota’s science fiction horror film The Brain Eaters. In the same year he was cast as the lead in Devil’s Partner, but the film was not released until 1962.

His television career featured many guest starring roles, such as the talented but arrogant Dr. Wade Parsons in the 1962 episode “Doctor on Horseback” of the NBC western series, The Tall Man, starring Barry Sullivan as Sheriff Pat Garrett and Clu Gulager as Billy the Kid. In the story line, Dr. Parsons works to save the life of a pregnant young woman who attempts suicide when her husband deserts her.  Nelson was cast in episodes of such other westerns as Maverick, Wagon Train, Black Saddle, Have Gun – Will Travel, The Rebel (five times), Johnny Ringo, Gunsmoke, Tombstone Territory, Laramie, Bonanza, Stoney Burke, The Dakotas, “The Rifleman” and Redigo.

He appeared on drama and adventure series too, such as The Fugitive, The Twilight Zone, The Outer Limits, Harbor Command, Tightrope, The Blue Angels (as the arrogant flight instructor Lieutenant Dayl Martin in “The Jarheads”), COronado 9, The Eleventh Hour, Thriller, and Channing, an ABC drama that romanticizes college life. He guest starred on Mission: Impossible and Jackie Cooper CBS military sitcom/drama, Hennesey.  He made two guest appearances on CBS’s Perry Mason, both times as the defendant; in 1961, he played Ward Nichols in “The Case of the Left-Handed Liar,” and in 1964, he played Dirk Blake, father of the title character, in “The Case of the Missing Button.”

In 1964, Nelson secured his most famous role portraying Dr. Rossi on the ABC drama Peyton Place, which ran from 1964 to 1969. Nelson’s fellow cast members included Mia Farrow, Ryan O’Neal, and Dorothy Malone. By 1968, all of the original stars had left the series, and Nelson became the lead actor on the show. Nelson reprised his role in two made-for-TV movies, Murder in Peyton Place and Peyton Place: The Next Generation.

Nelson, like other Peyton Place cast members disliked repeated reference to the series as a soap opera. “That kind of cheapens it. Not only were we on film, but we were outside all the time. You never see that on a soap,” Nelson said in a 2009 interview with The New York Times.  After Peyton Place, Nelson worked in many more productions of all varieties often as a guest star on such series as Gibbsville and Murder, She Wrote, and other starring roles in many movies of the week, including a second television series, The Silent Force, and a morning talk show,The Ed Nelson Show, that he hosted for three years.  In 1977, Nelson portrayed a dangerous impostor in the adventure film For the Love of Benji. During the 1980s, Nelson took on the role of Senator Mark Denning in the daytime soap opera Capitol.  Nelson also spent a couple of years playing U.S. President Harry S. Truman onstage, having replaced James Whitmore for the National Tour of “Give ‘Em Hell, Harry.”

While living in Los Angeles, Nelson was an active member of the Screen Actors Guild and was elected to the union board for many years. Nelson was a long-standing member of the Academy of Motion Picture Arts and Sciences and maintained a long tradition of participation in voting for the Academy Awards. He also served as the mayor of San Dimas, California for many years.  In 1999, Nelson returned to Tulane University to finish credits toward his undergraduate degree, which he completed the following year at the age of seventy-one. He and his wife, Patsy, enjoyed semi-retirement visiting his six children and fourteen grandchildren.  Nelson died on August 9, 2014 in Greensboro, North Carolina from congestive heart failure.