At the age of 16, he started working as an assistant to theatre Producer Kermit Bloomgarden. Later, he worked for producers Robert Whitehead and Emanuel Azenberg. In lieu of attending college, Rudin took a job as a casting Director and ended up starting his own company. His newly minted firm cast numerous Broadway shows, including Annie (1977) for Mike Nichols. He also cast PBS's Verna: USO Girl (1978), starring Sissy Spacek and william Hurt; and the mini-series The Scarlet Letter (1979) starring Meg Foster, Kevin Conway and John Heard; also, the films King of the Gypsies (1978), The Wanderers (1979), Simon (1980) with Alan Arkin and Resurrection (1980).

In 1980, Rudin moved to Los Angeles, taking up employment at Edgar J. Scherick Associates, where he served as Producer on a variety of films including I'm Dancing as Fast as I Can (1981), the NBC miniseries Little Gloria... Happy at Last (1982) and the Oscar-winning documentary He Makes Me Feel Like Dancin' (1983).

Rudin then formed his own company, Scott Rudin Productions. His first film under that banner was Gillian Armstrong's Mrs. Soffel (1984). Not long after, Rudin placed his production shingle in dormancy and joined 20th Century-Fox as an executive Producer. At Fox, he met Jonathan Dolgen, a higher-level executive, with whom he would be working once again at Paramount Pictures years later. Rudin rose through the ranks at Fox and became President of production by 1986 at the age of 29.

His stint at the top of Fox was short lived, and he soon left and entered into a producing deal with Paramount. On August 1, 1992, Rudin signed a deal with Tri-Star Pictures but soon moved back to Paramount. Rudin's first look deal with Paramount Pictures lasted nearly 15 years, producing pictures including Addams Family Values.

Rudin co-produced the unsuccessful staging of David Henry Hwang's Face Value with Stuart Ostrow and Jujamcyn Theaters. He started a deal with Jujamcyn to develop and produce new plays for the theater chain. In 1994, Rudin won the Best Musical Tony Award for his production of Stephen Sondheim and James Lapine's Passion. The following year, he, along with others, produced Kathleen Turner's Broadway comeback, Indiscretions, and Ralph Fiennes' New York theatre debut in Hamlet. In 1996, Rudin produced the revival of the Stephen Sondheim and Larry Gelbart musical A Funny Thing Happened on the Way to the Forum, which starred Nathan Lane, Ernie Sabella and Mark Linn-Baker.

He co-produced Edward Albee's The Goat or Who Is Sylvia? in 2002. He also produced Seven Guitars, The Ride Down Mt. Morgan, Copenhagen, Deuce, The History Boys, Beckett/Albee, Closer, The Blue Room, and Doubt. He co-produced the 2005 revival of Albee's Who's Afraid of Virginia Woolf? starring Kathleen Turner and Bill Irwin and directed by Anthony Page. In 2010, he co-produced, along with Carole Shorenstein Hays, the Broadway revival of August Wilson's Pulitzer Prize-winning play Fences, starring Denzel Washington and Viola Davis, which garnered ten Tony Award nominations and three wins, including Best Revival of a Play.

After the resignation of Paramount's chairwoman Sherry Lansing in 2004 and nearly simultaneous departure of Jonathan Dolgen (then President of the company), Rudin left the studio and set a five-year first-look pact with Disney that allowed him to make movies under their labels Touchstone Pictures, Walt Disney Pictures, Hollywood Pictures, and Miramax Films, whose founders Harvey and Bob Weinstein had departed. Previously, Harvey Weinstein and Rudin had public confrontations during the production of The Hours (2002), which Rudin produced for Miramax Films after it became a studio subsidiary under Disney. Rudin later said he and Weinstein "are both control freaks. We both want to run our own shows. When I'm doing a Miramax movie, I work for him. And I don't like that feeling. I chafe under that. I especially chafe under it when I feel that I'm on a leash."

In January 2008, two of Rudin's productions—the Coen brothers' No Country for Old Men, which they adapted from the Cormac McCarthy book of the same name, and Paul Thomas Anderson's There Will Be Blood, which was adapted from the Upton Sinclair novel, Oil!—were nominated for eight Oscars apiece at the 2008 Academy Awards, including a Best Picture nod for each of them. The two films shared the distinction of being the most nominated movie at that year's Oscar ceremony. Ultimately, No Country for Old Men won the Best Picture prize.

At the 2011 Producers Guild of America (PGA) Awards, Rudin became the only person ever to be nominated twice in one year. He was nominated (along with Dana Brunetti, Ceán Chaffin and Michael De Luca) for producing the Facebook biographical film The Social Network and was also nominated (along with Joel and Ethan Coen) for their remake of the classic western True Grit (2010). That same year, the PGA also awarded Rudin the David O. Selznick Achievement Award in Motion Pictures which recognizes an individual's outstanding body of work in the field of motion picture production.

On December 9, 2014, a major illegal breach of Sony's computer systems by "Guardians of Peace" hackers using Shamoon malware led to disclosure of many gigabytes of stolen information, including internal company documents. In subsequent news coverage SPE Co-Chair Amy Pascal and Scott Rudin were noted to have had an email exchange about Pascal's upcoming encounter with President Barack Obama that included characterizations described as racist. Both he and Pascal later apologized.

In 2015 Rudin produced Larry David's Fish in the Dark, a hit comedy that took in "more than $13.5 million in advance sales at the box office [which] beats the previous record for a play, $13.05 million for the 2013 revival of Harold Pinter's Betrayal," which was also a Rudin production.

Six Rudin productions received major Tony nominations in 2016. Nominated for Best Play were The Humans and King Charles III. Competing against Hamilton for Best Musical was Shuffle Along, or, the Making of the Musical Sensation of 1921 and All That Followed (with ten nominations, the second most after Hamilton). Three revivals were nominated for Best Revival: Blackbird, The Crucible and A View From the Bridge. Rudin was lead Producer on all the productions except King Charles III.

In 2017, Rudin produced a revival of Hello, Dolly! on Broadway with Bette Midler starring in the title role.