Bren is the son of Marion (Newbert) and Milton Bren. His Father Milton was a naval officer, talent agent, and successful movie Producer while his mother Marion was a prominent civic leader. His mother was of partial Irish descent while his Father was of Jewish descent. His parents divorced in 1948. Bren's Father remarried in 1948 to Academy Award-winning Actress Claire Trevor. His mother remarried in 1953 to steel Business man Earle M. Jorgensen.

Bren graduated from the University of Washington where he received a bachelor's degree in Business administration and economics. He tried out for the 1956 Olympic ski team but did not qualify following an injury. After college he served as an officer in the United States Marine Corps.

Bren built his first house in Newport Beach with a $10,000 loan, in 1958. He began his Business career in 1958 when he founded the Bren Company, which built homes in Orange County, California. In 1963, he and two others started the Mission Viejo Company (MVC) and purchased 10,000 acres to plan and develop the city of Mission Viejo, California. Bren was President of MVC from 1963 to 1967. International Paper bought Bren Co. for $34 million in 1970, and then sold it back to Bren for $22 million in 1972 following the recession. Bren took the proceeds and in 1977 joined a group of Investors to purchase the 146-year-old Irvine Company. Bren was the largest shareholder of the resulting consortium, owning 34.3% of the company and received the title of Vice-chair of the board. By 1983, he was the majority owner of the firm and was elected chairman of the board. By 1996, he had bought out all outstanding shares to become the sole owner.

In 1998, Bren received the Marine Corps University Foundation’s Semper Fidelis Award, which recognizes a distinguished American leader whose commitment to personal and professional excellence embodies those qualities of leadership and character uniquely associated with the United States Marine Corps. Past award recipients include former President George H.W. Bush and former Secretary of State George P. Schultz. The Foundation also presented Bren with its most prestigious award in 2003, the General Leonard F. Chapman Medallion named in honor of the 24th Commandant of the United States Marine Corps.

He has supported THINK Together, a provider of after-school services for K-12 students in Southern California. Bren first donated to this organization in 2001 with a contribution that helped the after-school program expand its services to 40 schools in the Santa Ana district. According to officials, the contribution would benefit more than 10,000 students over 10 years.

In 2003, Bren also donated $1 million to the Marine Corps University in Quantico, Virginia. The funds were used to endow two academic chairs focusing on ethics & leadership and innovation & transformation.

In 2004 Bren received the University of California Presidential Medal, the University’s highest honor, because of his financial support throughout the years which at the time was more than $43 million. During the award ceremony, former UC President, Robert Dynes said, “[Bren’s] passionate philanthropy and commitment to educational excellence have helped strengthen the university.”

Bren keeps a low public profile and as he explains, "I'm not a public official. I'm a businessman, I'm a builder, I'm a planner... And if I feel that I've done the job well, that's the satisfaction I get, not from doing interviews or being more public." OC Weekly described Bren in 2005 as "one of the nation's least public billionaires", who guards his privacy "jealously". The Los Angeles Times that year canceled a pending article discussing how the fictional Caleb Nichol of the popular television show The O.C. was based on Bren, allegedly because the Irvine Company threatened to withdraw advertising. The Times denied the allegation and stated that the story was canceled for timing reasons.

In 2006 the Los Angeles Times named Bren as both the most powerful and wealthiest person in Southern California, and the Orange County Business Journal named him “Businessperson of the Year” based on the company’s office expansion, new building construction, and Bren being recognized for his conservation efforts by the federal government. In 2011 the Urban Land Institute awarded Bren its first Vanguard Award, calling him "one of the most consequential developers in American history." In 2014 he was named on OC Register's list of the 100 most influential people in Orange County.

Bren serves on the board of trustees at Caltech and the Los Angeles County Museum of Art. He was elected a Fellow with the American Academy of Arts & Sciences in 2007 in the category of Business, Corporate and Philanthropic Leadership.

In 2008, the state of California also designated the land as the first California Natural Landmark because of the land’s ecological value. The protected land, once a part of Irvine Ranch, is operated by The Irvine Ranch Conservancy. Recently, Bren completed his pledge to set aside more than 50,000 acres of the original 93,000 acre ranch as open space by designating 20,000 acres (81 km2) to Orange County, California, as an open-space and parklands gift in June 2010. The gift was accepted in a unanimous decision by the Orange County Board of Supervisors and was the largest donation of private property to public ownership in Orange County history. In a ceremony in the same year, he was recognized for donating more than 20,000 acres of pristine wilderness that he gave to Orange County, asking only that it remain open space forever. In August 2014, the Irvine Company announced plans to donate and preserve 2,500 additional acres of land previously approved for housing, bringing the preserved lands of the Irvine Ranch to 60%.

In March 2009, he was ranked 9th in The (London) Sunday Times' "Green Rich List"—a list of the 100 wealthiest people who have either invested in green technology/businesses or made large contributions to environmental causes. Bren's placement on the list was due to his $20 million in donations to UC Santa Barbara's School of Environmental Science.

In 2010, Bren was honored with the National Philanthropy Day of Orange County “Donald Bren Legacy of Giving Award.” At the time Bren spoke about his work in philanthropy, saying that “I do try to bring the same level of attention to both my philanthropic and Business ventures.”

From a 2011 interview, solar Energy is one of the areas he is exploring for a Future philanthropic gift. "It's my view that solar Energy may be the ultimate solution for Energy for most of the world. I believe, based on what little I know about it, that there is a possibility of a breakthrough."

It is believed that the Irvine Company owns more than 120,000,000 ft.² of real estate – the majority of which is located in Southern California. The company's holdings include several hotels, marinas, golf courses, 550 office buildings, 125 apartment complexes and more than 40 shopping centers.

Gale Norton, former U.S. Secretary of the Interior, speaking about Bren’s history of land donations, said, “The Irvine Ranch illustrates what cooperative conservation is all about. A conservation-minded corporate citizen is working hand-in-hand with federal and state agencies, The Nature Conservancy, local communities, private citizens and other partners to thoughtfully and purposefully create an environment where both people and wildlife can thrive."