Born in New Orleans, Louisiana, Dedeaux attended the University of Southern California, and after playing professional baseball briefly - he appeared in 2 games as a shortstop for the 1935 Brooklyn Dodgers - he turned to playing and coaching in the semi-pro and amateur ranks. Meanwhile, in 1936 he and his father invested $500 to start a trucking firm, Dart (Dedeaux Automotive Repair and Transit) Enterprises, which he successfully built into a thriving regional business. When his college coach Sam Barry entered the United States Navy during World War II, he recommended Dedeaux to take over the team in 1942 for the war's duration, and upon Barry's return in 1946 they served as co-coaches, with Dedeaux running the team each year until Barry finished the basketball season. The arrangement was so successful that USC won the College World Series in 1948.

After Barry's death in September 1950, Dedeaux became the sole coach, and proceeded to build on the early success to establish the strongest program in collegiate baseball. Prior to his retirement in 1986, Dedeaux's teams won 10 additional CWS titles - no other coach won more than 3 until 1997 - including five consecutively from 1970-1974. He also developed dozens of future major leaguers, including Ron Fairly, Don Buford, Tom Seaver, Dave Kingman, Roy Smalley, Fred Lynn, Mark McGwire and Randy Johnson. Throughout his USC career, he accepted only a nominal salary of $1 per year, as his trucking business supplied a substantial income. He turned down numerous offers of major league coaching positions, including invitations from Los Angeles Dodgers manager Tommy Lasorda to join his staff, but always rejected them due to his preference for the college game and his desire to remain close to his family.

He served as coach of the United States team at both the 1964 Summer Olympics in Tokyo, Japan and the 1984 Summer Olympics in Los Angeles, with baseball being a demonstration sport prior to its elevation to full medal status in 1988. He retired as the winningest coach in college baseball history with 1,332 victories, and for the rest of his life remained a beloved annual presence at the College World Series in Omaha, Nebraska. He was inducted into the American Baseball Coaches Association's Hall of Fame in 1970, and in 1999 was named the Coach of the Century by Collegiate Baseball magazine.

With USC playing its home games at Bovard Field, Dedeaux became known as "The Houdini of Bovard" for its come-from-behind home-field wins. In 1974 USC constructed a new baseball field named Dedeaux Field in honor of the coach.

Dedeaux also served as the baseball coach for actors and ballplayers on the film Field of Dreams (1989). Phil Alden Robinson, who directed the film, said the following about Dedeaux:

"All of the ballplayers in the movie were prepped for the film by Rod Dedeaux. He coached at USC for many years, and is a wonderful man, very full of life, energetic, very supportive, just really was very giving of himself and cheerful all the time, was a great spirit to have around. And one day, we were in between setups and I said, Hey, coach, what position did you play? He said, I was a shortstop. I said, Really, could you -- were you good? He got very quiet, and he said, I could field the ball. I said, Could you hit? He said, I could hit the ball. And he was strangely quiet. And I said to him, Well, how come you never played in the majors? And he said, I did. I said, Really. Yes, in 1930-something. I forget what year he said. He was the starting shortstop for the Brooklyn Dodgers. He played one game, broke his back, and that was the end of his career. And I just blanched. I said, My God, you're Doc Graham. He said, That's right. And I said, Do you ever think about, gee, the career I might've had. And he said, Every day. He said it very quietly. It was very out of character for him, and I was so touched by that. And I did look him up in the Baseball Encyclopedia: He did go, I think, 1-for-4 with an RBI. That was his lifetime stats. So having him be the man who trained all these fellows, including the kid who plays Doc Graham, was very meaningful to me, and I know it was to him, too. It was great to have him around. I think about that often, about what that must have been like, to be good enough to start with a Major League team, and for one unlucky moment, not be able to do -- the rest of your life takes another turn. What he did with that is, he put all of that emotion -- which could have gone into bitterness or regret -- into being a phenomenal coach. He sent more people to the majors than, I think, anybody else in college history. He's an amazing man." (Source: Director's commentary recorded for the anniversary edition DVD of Field of Dreams) Dedeaux died at age 91 in Glendale, California of complications from a December 2, 2005 stroke. He was survived by his wife of 66 years, the former Helen Jones, and their four children.