Morello was born in 1924 in Marseilles, Illinois. In 1954, she earned a master's degree in African and Latin American history at Loyola University in Chicago. She spent the rest of the decade teaching English in Germany, Spain, and Japan while once circling the globe on a freighter.
From 1960 to 1963, she lived in Kenya where she married Kenyan revolutionary Ngethe Njoroge, who later became the first Kenyan delegate to the United Nations. He was a guerrilla in the Mau Mau Uprising (1950–1960) that arguably led to Kenya's independence from British rule.
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, where she gave birth to their son, Tom Morello.
Mary and Ngethe divorced when Tom was one year old in 1965. Morello then moved with her son to Libertyville, Illinois, a small suburb north of Chicago. She took a job at Libertyville High School teaching social studies and US history. In 1987, she quit her teaching job of twenty-two years and founded Parents for Rock and Rap, an anti-censorship counterweight to Tipper Gore's Parents Music Resource Center.
In 1991, she 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 in Arts and Entertainment for her work with Parents for Rock and Rap.
In the fall of 1991, she began a volunteer teaching job at the Salvation Army Rehabilitation Center in Waukegan, Illinois, where she taught adult literacy. She was involved in the Cuba Coalition in Chicago, which works toward lifting the U.S. embargo against Cuba.
In a Rage Against the Machine concert in 1994, she introduced them as the "Best Band in the ####### Universe". 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 f***ing band in the universe.”
She is also known for her involvement in the 1999 debate on the incarceration of death row inmate Mumia Abu-Jamal, convicted (some believe wrongly) of the 1982 shooting of a Philadelphia police 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."
- "The Mary Morello and Cindy Sheehan Show" (episode 06). Axis of Justice. August 6, 2007. Archived from the original on 2007-12-11. Retrieved 2008-01-09.
- "Tom Morello". SEIU.org. 2007. Archived from the original on 2008-03-11. Retrieved 2008-01-09.
- Holthouse, David (September 26, 1996). "Bottled Anger Rage Against the Machine guitarist Tom Morello pours forth the vitriol". Phoenix New Times. Retrieved 2008-01-09.
- Beaubien, Greg (August 23, 1995). "Freedom Fighter: 71-Year-Old Mary Morello Vigorously Campaigns For Rock 'n' Roll's Right To Rap Free". Chicago Tribune. Archived from the original on 2004-12-20. Retrieved 2008-01-09.
- Johnson, Kevin (2003). "PARENTS FOR ROCK & RAP". Rock Out Censorship. Retrieved 2008-01-09.
- "BCFE Names 1995/1996 Heroes and Villains". Electronic Frontier Foundation. 1996. Retrieved 2008-01-09.
- DiNovella, Elizabeth. "Tom Morello Interview". The Progressive Magazine. Retrieved 2008-01-09.
- "Prophets Of Rage Pay Tribute To Kaepernick At Shoreline Concert". Retrieved 2016-09-14.
- Morello, Mary (November 1999). "Guest Editorial By Mary Morello". Volume 3, Issue 1. The Microphone: The Mass Mic Newsletter. Retrieved 2008-01-09.
- "The Mary Morello and Cindy Sheehan Show". Axis of Justice. Retrieved 2008-01-09.