Holleder was born in Buffalo, New York, and at age 13, he and his family moved to Irondequoit, New York. He attended high school at the Aquinas Institute in nearby Rochester. He was heavily recruited by a number of top college football teams, including West Point's offensive coach Vince Lombardi. He elected to enroll at the United States Military Academy at West Point. As a junior in 1954, he was named to the All-America team as an end. The following season, Army head coach Red Blaik asked him to move to quarterback. Holleder clearly lacked the skills to be a productive passer, but Blaik felt that his leadership skills were important and would help the struggling team improve. Blaik's move was ridiculed but it paid off. The team finished with a record of 6-3-0, including a rousing upset of Navy that led to Holleder's appearance on the cover of Sports Illustrated. One of Holleder's classmates at West Point was Norman Schwarzkopf. They both graduated in 1956.
The New York Giants selected Holleder in the 1956 NFL Draft college draft, but Holleder was not interested in a professional football career. After graduating West Point, he continued to serve in the US Army. Over the next ten years he rose to the rank of Major, serving posts in Hawaii and Korea, and in between returning to West Point for three years as an assistant football coach, recruiter, and scout.
In 1967, Holleder, now a major, requested to be sent to Vietnam, where he became the Operations Officer for 1st Brigade of the 1st Infantry Division. He was killed in the Battle of Ong Thanh on October 17, 1967. While he and his commanding officer were overflying the battle in a helicopter, they observed that the entire command unit on the ground had been killed and the remaining men were in serious trouble. Don volunteered to organize a rescue effort. Upon landing, Don secured three volunteers and rushed to the battle site. Running far in front of his volunteers, he was gunned down and killed by a sniper. The battle is documented in Pulitzer Prize-winning reporter David Maraniss’ book They Marched Into Sunlight and Terry Tibbetts' book A Spartan Game, the Life and Loss of Don Holleder. A film of the story is being produced by Tom Hanks.
Holleder left behind a wife and four children.
In 1974, the football stadium in his hometown was renamed Holleder Memorial Stadium in his honor. The stadium was home to the football team of his high school Alma Mater,Aquinas Institute. In 1985 the stadium was torn down. The Holleder Technology Park now stands on the site, bisected by Holleder Parkway.
In 1985, he was inducted into the College Football Hall of Fame, and that same year, West Point's basketball/hockey arena was named in his honor (The Donald W. Holleder Center). Each year, the Army football team recognizes one of their players with the Black Lion Award, given "to a player who best exemplifies the character of Don Holleder, leadership, courage, devotion to duty, self sacrifice and, above all, an unselfish concern to put the team ahead of himself."
He was posthumously awarded the Distinguished Service Cross on April 27, 2012