[8] During childhood, her father, a low-budget independent filmmaker, introduced Mimi and her siblings to film production.

Leder began her career as a second unit director on her father's 1976 film A*P*E, then as a script supervisor on a string of films, including Spawn of the Slithis (1978), Dummy (1979), The Boy Who Drank Too Much (1980), and A Long Way Home (1980) and then moved to the TV series Hill Street Blues (1981).

She made the made-for-TV films Woman with a Past (1992), House of Secrets (1993), and Baby Brokers (1994), then became one of the core directors for ER (1994–2009).

Continuing to work for DreamWorks, she directed Deep Impact (1998) and Pay It Forward (2000) while simultaneously creating Sentimental Journey (1999), a personal love story about her parents.

When asked for a reaction about her film Deep Impact (1998) vs. a rival movie release at the same time Armageddon (1998), she responded: "Michael Bay did come to my premiere, which really shocked me.

She shot nine pilots and produced six series, including The Beast (2001), John Doe (2002), Johnny Zero (2005), and Vanished (2006).

Leder's feature film On the Basis of Sex, the story of Ruth Bader Ginsburg's path to become a U.S. Supreme Court Justice, was released in December 2018.