Brolin was raised in the Westwood area of Los Angeles, not far from 20th Century Fox, the studio where he began in show business, first aspiring to be a cinematographer or director. But the studio soon put him under contract as an actor, and he made his debut in an episode of the TV series "Bus Stop" (ABC, 1961), and in a bit in the feature generational comedy "Take Her, She's Mine" (1963). He continued in small parts in Fox productions (including a recurring role on the 1966-67 ABC TV series "The Monroes" and as a private in the 1965 Frank Sinatra movie, "Von Ryan's Express") until 1967, when he got his first leading role opposite Jacqueline Bisset in a movie in "The Cape Town Affair", the remake of Sam Fuller's 1953 racially-charged "Pick-Up on South Street".

Brolin's feature career failed to ignite, and he moved to Universal Studios, where he was cast as Dr. Kiley, the highly-trained young physician who dreamed of a high-powered career but ended up sharing a practice with an aging but kindly general practitioner (Robert Young) in the 1969 TV-movie/pilot for "Marcus, Welby, M.D." Brolin won an Emmy for his work in 1970 and became a TV star. He was immediately cast in several TV-movies, including "Short Walk to Daylight" (ABC, 1972) and "Trapped" (ABC, 1973), the latter was the highest-rated TV-movie of that season, thanks in no small measure to Brolin's popularity.

Brolin attempted a feature film career after the demise of the series. It was hoped his big break would be as Clark Gable opposite Jill Clayburgh in "Gable and Lombard" (1976), but his work as "The King" failed to impress critics and did not meet the expectations of Gable's fans. Within a year, Brolin found himself in "The Car" (1977), as a cop battling an automobile possessed by the devil. In 1979, he was in another horror picture, "The Amityville Horror", as the terrorized head of the household. The film became the then-highest-grossing independent feature film to date. His subsequent big screen outings were generally dismissed by both audiences and critics (the exception was Allison Anders' 1992 "Gas Food Lodging").

In 1983, Brolin returned to series TV as Peter McDermott, the general manager of the fictional St. Gregory Hotel in San Francisco on "Hotel". While the ABC series was anthological in nature, McDermott did end up in a romance with his assistant, portrayed by Connie Sellecca. The series had a five-year run, during which Brolin directed many of the episodes. After it was canceled, Brolin hosted the syndicated reality series "Reunion" (1990), in which past loves found each other again. He followed with work on two short-lived series, the primetime soap "Angel Falls" (CBS, 1993) and "Extreme" (ABC, 1995), which had been described in the press as "'Baywatch' on skis." He returned to the small screen as star of the syndicated action series "Pensacola: Wings of Gold" in 1997.

Brolin has also to appear in longforms, including the 1991 CBS miniseries "And the Sea Will Tell", based on the book by attorney Vincent Bugliosi. Additionally, Brolin directed episodes of the ABC series "The Young Riders", which starred his son, Josh Brolin. The younger Brolin also appeared in his father's feature directorial debut, the direct-to-video release "My Brother's War" (1998), about the Irish Republican Army. Perhaps after rubbing elbows with his wife Barbra Streisand's A-List friends, Brolin's career heated up again. He played a small but important role in director Steven Soderberg's acclaimed ensemble drama "Traffic" (2000), and appeared as a businessman who gets in the middle of Leonardo DiCaprio's family in "Catch Me If You Can" (2002). He also played against type in wacky comedies, appearing as Dana Carvey super-spy dad in "Master of Disguise" (2002) and playing Selma Blair's shotgun-toting father in "A Guy Thing" (2003).