Ladd was born Rose Diane Ladner in Meridian, Mississippi, the only child of Mary Bernadette (née Anderson; 1912–2002), a housewife and actress, and Preston Paul Ladner (1905–1982), a veterinarian who sold products for poultry and livestock. Ladd is related to playwright Tennessee Williams and poet Sidney Lanier. Ladd was raised in the Roman Catholic faith of her mother.
Ladd was married to actor and one-time co-star Bruce Dern from 1960 to 1969, and had two daughters, including Diane Elizabeth Dern, who died at seventeen and a half months, and actress Laura Dern. Ladd and Laura Dern co-starred in the films, Wild at Heart, Rambling Rose and Inland Empire, and in the HBO series Enlightened.
Ladd is currently married to Robert Charles Hunter.
In 1971, Ladd joined the cast of the CBS soap opera, The Secret Storm. She was the second actress to play the role of Kitty Styles on the long-running daytime serial. She later had a supporting role in Roman Polanski's 1974 film Chinatown, and was nominated for an Academy Award for Best Actress in a Supporting Role for her role as Flo in the film Alice Doesn't Live Here Anymore. That film inspired the television series Alice, in which Flo was portrayed by Polly Holliday. When Holliday left the TV series, Ladd succeeded her as waitress Isabelle "Belle" Dupree.
She appeared in the independent screwball comedy Hold Me, Thrill Me, Kiss Me in 1992, where she played a flirty, aging Southern belle alongside her real mother, actress Mary Lanier.
In 1993, Ladd appeared in the episode "Guess Who's Coming to Chow?" of the CBS comedy/western series Harts of the West in the role of the mother of co-star Harley Jane Kozak. The 15-episode program, set on a dude ranch in Nevada starred Beau Bridges and Lloyd Bridges.
In 2004, Ladd played psychic Mrs. Druse in the television miniseries of Stephen King's Kingdom Hospital. In April 2006, Ladd released her first book, Spiraling Through The School of Life: A Mental, Physical, and Spiritual Discovery. In 2007, she co-starred in the Lifetime Television film Montana Sky.
In addition to her Academy Award nomination for Alice Doesn't Live Here Anymore, she was also nominated (again in the Best Actress in a Supporting Role category) for both Wild at Heart and Rambling Rose, both of which she starred alongside her daughter Laura Dern. Dern received a nomination for Best Actress for Rambling Rose. The dual mother and daughter nominations for Ladd and Dern in Rambling Rose marked the first time in Academy Award history that such an event had occurred. They were also nominated for dual Golden Globe Awards in the same year.
Ladd has also worked in onstage. She made her Broadway debut in Carry Me Back to Morningside Heights in 1968. In 1976, she starred in A Texas Trilogy: Lu Ann Hampton Laverty Oberlander, for which she received a Drama Desk Award nomination.
She currently stars in the Hallmark Channel series Chesapeake Shores.
Note: Alice Doesn't Live Here Anymore released in 1974 in the US and 1975 in the UK.
On November 1, 2010, Ladd, Laura Dern, and Bruce Dern received adjoining stars on the Hollywood Walk of Fame; this is the first time family members have been given such consideration on the Walk. Ladd's star is the 2,421st.