As Donner worked in Los Angeles as an assistant editor of educational and medical films, she sought other jobs and despite having no original intention to work in television, a chance meeting at NBC headquarters led her to leave her data there. In 1973, the network invited Shuler to a vacation relief program filling in for employees on vacation. She worked on many jobs, but decided that the best for her would be as a camera operator due to her photography experience. After being taught about cameras by the crew of The Tonight Show, Shuler asked NBC to work on the local news. Afterwards she freelanced on Metromedia, working on rock concert shoots, sitcoms and TV movies. Donner was a rare camerawoman in a male-dominated field, being the first woman admitted to the IATSE Electrical and Camera Guild #659.

Eventually Donner decided to work as an associate producer, in 1976 joining ABC’s Wide World of Entertainment. After a traffic accident that had her hospitalized for months, Donner started working with screenwriter friends and became a creative executive/story editor on Motown Productions. Her input on the script of Thank God It’s Friday (1978) led her to become an associate producer for that film. Next she made her television producing debut in 1979 with the acclaimed Amateur Night at the Dixie Bar and Grill, a television film written and directed by Joel Schumacher in the style of Robert Altman’s Nashville. She got the job by directly asking NBC programming director Charles Engel.

While working at Motown, Donner became a personal friend of National Lampoon writer John Hughes, and convinced him to write a script that would become her feature film producing debut, the 1983 comedy hit Mr. Mom, starring Michael Keaton. The following year she persuaded Richard Donner to direct Ladyhawke, and the two fell in love, marrying a year after the film was released, 1985. She produced only two more of her husband’s movies, Radio Flyer (1992), and Timeline (2003). She said their professional relationship helped her learn how to work on action films: “if I hadn’t seen how he did action movies, I wouldn’t have had the wherewithal to even pursue an X-Men or a Constantine, or any of those”. Her experience with Schumacher and Hughes led them to invite her to produce St. Elmo’s Fire (1985) and Pretty in Pink (1986), both seminal films of the Brat Pack period. Donner had a particularly successful year in 1993 overseeing two solid hits: Dave, a homespun political comedy, and Free Willy, a family film about a boy and his whale. While Donner has credits in all X-Men films, the last ones she actually produced were X-Men: Days of Future Past and Deadpool; Simon Kinberg took over the later films so Donner could instead make the TV show Legion, with Donner only receiving producer credit out of loyalty.

Donner has received a star on the Hollywood Walk of Fame in 2008, right next to her husband’s. In 2006, Donner was awarded the Women in Film Crystal Award along with Jennifer Lopez and Diane Warren. She received an honorary Doctorate of Human Letters degree from Boston University in 2019 and was the Commencement Speaker for COM at Boston University. She and Richard Donner were honored by The American Cancer Society in 2006. The Donners were given The Loop Award by LupusLA in 2008. The Donners were also given a Lifetime Achievement Award from The Ojai Film Festival in November 2008. In 2013, the Donners were honored by The Women’s Guild of Cedar Sinai Hospital.