He is the son of Hollywood producer Milton Bren. He attended the University of Washington, where he was a member of Beta Theta Pi, on a ski scholarship and tried out for the Olympic team in 1956. He holds a degree in business administration and economics. After college he served in the Marines.

In 1977 Bren joined a group of 34 investors to purchase the Irvine Company. By 1996, he had bought out all outstanding shares to become the sole owner.

Forbes magazine, in its 2005 edition of the 400 Richest People in America, ranked Bren as the wealthiest real estate owner in the US with an estimated net worth of $5.7 billion.

He is a donor to many Orange County institutions, including University of California, Irvine, Chapman University, and The Orange County Museum of Art. At UCI, the Bren Events Center and the Donald Bren School of Information and Computer Science are named after him due to his patronage of the school. At the University of California, Santa Barbara, the Donald Bren School of Environmental Science & Management is named after him.