In the 1960s, Morello was involved in the Civil Rights movement and the NAACP. She is a long-time activist for the Chicago Urban League. In 1964, she and her husband moved to Harlem, New York,[5] where she gave birth to their son, Tom.
In 1991, Morello and many others battled against legislation being proposed in Congress titled Pornography Victims Compensation Act, numbered S. 983, or, later, S. 1521. The legislation was not enacted, in part because of grass-roots activism. On June 24, 1996, she received the Hugh M. Hefner First Amendment Award[7] in Arts and Entertainment for her work with Parents for Rock and Rap.
Morello is also known for her involvement in the 1999 debate on the incarceration of death row inmate Mumia Abu-Jamal, convicted of the 1982 shooting of a Philadelphiapolice officer. In an editorial, she said:
"When a cop is shot someone must be found guilty. As my son Tom says, '...all rational thinking goes out the window'. A cop being killed is no different than any other person being killed. They choose their profession."[9]
In 2007, Morello had a podcast together with Cindy Sheehan called The Mary Morello and Cindy Sheehan Show.[10]
Before Rage Against the Machine hit the stage at the Pinkpop Festival in 1994, Morello introduced them as the "Best Band in the Fucking Universe".[13] On August 24, 2007, for the Rage Against the Machine reunion, she appeared again. On September 13, 2016, at a Prophets of Rage concert, she introduced them as "The best fucking band in the universe."[14][15]