Broad was born in 1933 in the Bronx, New York, the only child of Lithuanian Jewish immigrant parents who met in New York. His Father worked as a house Painter, and his mother worked as a dressmaker. His family moved to Detroit, Michigan when he was six years old. In Detroit, his Father was a union organizer, and owned five-and-dime stores. Broad attended Detroit Public Schools and graduated from Detroit Central High School in 1951.

Broad attended Michigan State University, majoring in accounting with a minor in economics and graduating cum laude in 1954. Among the jobs Broad held in college were selling women's shoes, selling garbage disposals door-to-door, and working as a drill press operator at Packard Motor, where he was a member of United Auto Workers. The same year, 21-year-old Broad married 18-year-old Edythe "Edye" Lawson.

Doing the accounting for Kaufman's small Business led Broad to decide to enter homebuilding himself. In 1956, Broad and Kaufman decided to partner and build homes together. Borrowing $12,500 from his wife's parents, Broad put up half the capital in their first venture together, building two model homes in the Northeast Detroit suburbs where a new generation of first-time home buyers were flocking. By streamlining the construction process and eliminating basements, offering a carport instead, they could price the houses so the monthly mortgage would be less than the rent for a two-bedroom apartment. Kaufman and Broad christened this model the "Award Winner" and priced it at $13,700. After one weekend, seventeen were sold and within two years, Kaufman and Broad had built 600 homes in the Detroit suburbs. In 1960, fearing that the Detroit economy was too dependent on the Automotive Business, they moved to Phoenix, Arizona. In 1961, Kaufman and Broad Home Corporation (now KB Home) went public on the American Stock Exchange. In 1963, Broad moved the company to Los Angeles. Soon after, Kaufman retired and he and his wife Glorya Kaufman went on to become noted Philanthropists. By 1969, KB Home was the first homebuilder listed on the New York Stock Exchange. In 1974, Broad stepped down as CEO.

In 1971, Broad acquired Sun Life Insurance Company of America, a family-owned insurance company founded in Baltimore in 1890, for $52 million. Broad transformed Sun Life into the retirement savings powerhouse SunAmerica. In 1999, he sold SunAmerica to the American International Group (AIG) for $18 billion. Broad continued as CEO of SunAmerica until 1999, when he left to focus on philanthropy full-time.

Broad has been an influential figure in the art world since 1973 and has had a particular focus on the cultural life of Los Angeles.

Broad was the founding chairman of the Museum of Contemporary Art, Los Angeles in 1979 and chaired the board until 1984. He recruited the founding Director of the museum and negotiated the acquisition of the Panza Collection for the museum.

Eli and Edythe Broad established The Broad Art Foundation in 1984 with the goal of making their extensive contemporary art collection more accessible to the public; to date The Foundation has made more than 8,000 loans to more than 500 museums and university galleries worldwide.

In 1991, Broad endowed the Eli Broad College of Business and the Eli Broad Graduate School of Management with $20 million for a full-time MBA program at his alma mater, Michigan State University. The couple gave $5 million to endow the Eli and Edythe L. Broad Dean of Business.

Broad founded the Grand Avenue Committee, which coordinates and oversees development of Grand Avenue in downtown Los Angeles. In 1996, Broad and Los Angeles Mayor richard Riordan led the fundraising campaign to build the Frank Gehry-designed Walt Disney Concert Hall, which opened in October 2003. Broad was instrumental in securing the $50 million deposit from the project developer that opened Grand Park in summer 2012.

The stated mission of the Eli and Edythe Broad Foundation's education work is to ensure that every student in an urban public school has the opportunity to succeed. The foundation has made $589 million in grants since it launched in 1999.

In 2000, Broad gave $23.2 million for the Broad Art Center at UCLA, designed by Richard Meier. Eli and Edythe Broad donated $28 million to Michigan State University for the construction of the Eli and Edythe Broad Art Museum, designed by Pritzker Architecture Prize-winning Architect Zaha Hadid. The museum opened in November 2012.

In 2001, the Broads created the Broad Medical Research Program to fund innovative research to advance the treatment of IBD.

From 2002 to 2014, The Broad Foundation awarded an annual $1 million Broad Prize for Urban Education. The Broad Prize recognized the large urban school districts in America that have made the greatest improvement in student achievement while narrowing achievement gaps among low-income students and students of color. The Broad Prize has awarded $16 million in college scholarships to high school seniors since 2002. In 2012, the foundation launched the Broad Prize for Public Charter Schools, which awards $250,000 to the top charter management organization in the country. In 2015, the foundation announced that it was suspending the Broad Prize for Urban Education.

In 2003, Eli and Edythe Broad gave the $100 million founding gift to create The Broad Institute of MIT and Harvard. The following year, they gave another $100 million, and in 2009, they gave another $400 million to create an endowment to make the institute permanent. The Broads announced Nov. 14, 2013, they were giving an additional $100 million to the institute. The Broad Institute is now the leading genomic Medicine institute, employing 2,000 people with an annual research budget of $287 million. To date, the Broads have given $800 million to the Institute.

From 2004 to 2009, Broad served as a Regent of the Smithsonian Institution by appointment of the U.S. Congress and the President. He is a Fellow of the American Academy of Arts and Sciences and in 1994 was named Chevalier in the National Order of the Legion of Honor by the Republic of France. Broad serves on the board of the Future Generation Art Prize. He received the Carnegie Medal of Philanthropy in 2007 and the David Rockefeller Award from the Museum of Modern Art in March 2009. In October 2013, the Broads were awarded the william E. Simon Prize for Philanthropic Leadership by Philanthropy Roundtable.

The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC is the product of a public-private partnership between voter-created California Institute of Regenerative Medicine, the Keck School of Medicine of USC and the Eli and Edythe Broad Foundation, which donated $30 million in 2006. In 2007, the Broads also donated $20 million to the UCLA Stem Cell Institute. One year later, they gave a major gift to the University of California, San Francisco for the new headquarters of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, which opened in February 2011. Broad is also a member of the California Institute of Technology Board of Trustees where he funded the Broad Center for the Biological Sciences. In 2009, the Broads gave $5 million to fund the Joint Center for Translational Medicine at Caltech and UCLA.

The Broads contributed $10 million in 2008 for a programming endowment for a state-of-the-art music and performing arts center at Santa Monica College, The Eli and Edythe Broad Stage, and an adjacent black box performance space, The Edye.

The Broads provided the lead gift of $6 million to the Los Angeles Opera to bring richard Wagner's opera cycle Der Ring des Nibelungen to Los Angeles for the 2009–10 season. In June 2013, the Broads gave $7 million to continue funding the Eli and Edythe Broad general Director at L.A. Opera, currently occupied by Plácido Domingo.

In August 2010, Eli Broad announced formally that he would build a contemporary art museum in Downtown Los Angeles. Diller Scofidio + Renfro were chosen through an architectural competition to design the approximately 120,000-square-foot museum, which includes exhibition space, offices and a parking garage.

In 2012, Broad's first book, The Art of Being Unreasonable: Lessons in Unconventional Thinking, was published by Wiley and Sons and debuted as a New York Times, Wall Street Journal, USA Today, and Washington Post bestseller.

In August 2013, Broad donated $250,000 to oppose the recalls of Colorado Senate President John Morse and Sen. Angela Giron, who were being recalled for their support of gun control measures, including a ban on magazines of 15 rounds or more.

The Broads have two collections—a personal collection with nearly 600 works and The Broad Art Foundation's collection, which has approximately 1,500 works Modern and contemporary art. In January 2008, the Broads decided that works in their personal collection would ultimately go to their foundation to make the artwork accessible to the public through the foundation’s loan program.

In February 2015, a public preview of a special installation attracted some 3,500 visitors while the museum was still under construction. The museum opened by Broad and his wife on Sunday, September 20, 2015. To date, it has received more than 1.2 million visitors.

In 2017, Broad announced his retirement from The Eli and Edythe Broad Foundation, passing responsibility to its President, Gerun Riley. Broad said he would remain as a trustee of the foundation, and continue to serve on the Board of The Broad museum. Broad said he was in good health and felt like it was time to "step back".

The Los Angeles Times obtained a secret 44-page proposal drafted by the Eli and Edythe Broad Foundation and other charter advocates, that according to one critic would "do away with democratically controlled, publicly accountable education in LA." With the aid of a billionaires’ club of supporters, the plan is designed to charterize 50% of LA public schools."