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Born in St. Petersburg, Florida, Yeshitela participated in the American Civil Rights Movement in his youth during the 1950s and 1960s as a member of the Student Nonviolent Coordinating Committee. At the height of the civil rights movement in St. Petersburg, Waller was jailed for an act of civil disobedience in 1966, when he tore a mural in City Hall depicting degrading caricatures of African Americans. Waller spent two and a half years in jail and prison. After his release, he was stripped of his right to vote for decades until Governor Jeb Bush and three members of Florida's Cabinet restored his voting rights in 2000.
In his civic activism in his native St. Petersburg, Yeshitela has stressed his view that political and economic development will bring peace to African-American neighborhoods. He moved to Oakland, California in 1981, living and working there.
Yeshitela came under national attention in October–November 1996 when civil disturbances in predominantly African-American South St. Petersburg were triggered by the police killing of Tyron Lewis, an 18-year-old African-American motorist who had attempted to kill a police officer with a car. Yeshitela condemned the killing as the culmination of a long pattern of repressive and racist measures by the St. Petersburg Police Department in African American neighborhoods, and rallied support for the victim's family in the black community. As a result of the community outcry, the city came under federal scrutiny, leading to a meeting between Yeshitela and HUD Secretary Henry Cisneros, who was sent to the city by President Bill Clinton in answer to the disturbances. After meeting with the veteran civil rights leader, Cisneros warned the city council that the African-American community's problems with the police were deeply rooted and that the demands of the community must be heard and called Yeshitela one of the most "admirable leadership figures" he had ever encountered.  According to the former HUD Secretary, Yeshitela is "a person who touches lives in a serious way." "I found him a thoughtful person who had some important things to say," said Cisneros.
Yeshitela served on St. Petersburg Mayor David Fischer's Challenge 2001 Steering Committee and on the St. Petersburg Housing Authority's Hope VI Advisory Committee, two projects dedicated to attracting jobs and investment to South St. Petersburg. He has also chaired the political action committee of the Coalition of African American Leadership, made up of a number of black churches and civil rights groups in the area, and served on the board of radio station WMNF community radio. Along with eight other candidates, Yeshitela made a run for mayorship in February 2001. Although he did not make it to the runoff, he won every African-American and mixed precinct but one in the entire city.
Yeshitela is also the founder of Citizens United for a Shared Prosperity.
The Uhuru Movement refers to a group of organizations under the principle of "African internationalism," or the liberation of Africans in both the continent of Africa and in the African Diaspora. 'Uhuru' is a Swahili word for freedom. The Movement is led by Yeshitela's African People's Socialist Party (APSP).
The APSP has formed several organizations, each with specific tasks and purpose. Affiliated organizations include The International People's Democratic Uhuru Movement, African Socialist International, African People's Solidarity Committee, and Burning Spear Productions, the African People's Education and Defense fund and the All African People's Development and Empowerment Project.
In May 1972, after his release from prison, Yeshitela founded the St. Petersburg-based African People's Socialist Party (APSP), a political party founded on an ideology combining black nationalism and socialism called "African internationalism."  Yeshitela later set up an organization for white people to join in solidarity with the APSP's goals, the African People's Solidarity Committee.
Later, the APSP formed the International People's Democratic Uhuru Movement to work under the guiding principle that the only way for Africans to achieve liberation and self-determination is to struggle for an all-African socialist government under the leadership of African workers and poor peasants.
Yeshitela has also established the African People's Education and Defense Fund, which seeks to address disparities in education and health faced by African Africans, and Burning Spear Productions, the publishing arm of the APSP.
The APSP is affiliated with the African Socialist International, an organization Yeshitela helped establish that seeks to unite African socialists and national liberation movements under a single revolutionary umbrella in opposition to imperialism and neocolonialism.
He calls for reparations for the black community. Yeshitela has set up a coalition promoting reparations for slavery, arguing that African people worldwide are due reparations for more than slavery, but also over 500 years of colonialism and neocolonialism. 
Self-published with Burning Spear Uhuru Publications / African People's Socialist Party:
- One Africa! One Nation! (2006), ISBN 978-1-891624-04-9
- Omali Yeshitela Speaks: African Internationalism, Political Theory for our Time (2005) ISBN 978-1-891624-03-2
- Social Justice and Economic Development for the African Community: Why I became a Revolutionary (1997)
- The Dialectics of Black Revolution: The Struggle to Defeat the Counterinsurgency in the U.S. (1997)
- Izwe Lethu i Afrika! (Africa is Our Land) (1991)
- On African internationalism (1978)
- Tactics and Strategy for Black Liberation in the US, 1978
- The Struggle for Bread, Peace and Black Power, 1981
- Stolen Black Labor, 1982
- Reparations Now!, 1983
- A New Beginning and Not One Step Backwards,1984
- The Road to Socialism is Painted Black, 1987
- Overturning the Culture of Violence, by Penny Hess and Omali Yeshitela, 2000 (ISBN 978-1891624025)
- One People! One Party! One Destiny!, 2010 (ISBN 978-1891624070)
- Enhancing Police Integrity, by Carl B. Klockars, Sanja Kutnjak Ivković, Maria R. Haberfeld, 2006 (ISBN 978-0-387-36954-9).
- "Uhuru Are You? Meet the little-known black power group behind a well-known institution", by Tom Dreisbach, Philadelphia Citypaper, August 12, 2009.
- "Officials in St. Petersburg Call Racial Unrest 'Calculated'", by Mireya Navarro, New York Times, November 15, 1996.
- "Effort to Heal Old Racial Wounds Brings New Discord", by Rick Bragg, New York Times, July 3, 1999.
- "NAACP-Connected Black Radical Praises Connecticut Mass-Murderer", by David Stein, Yes, But However!, August 12, 2010.
- Official Website of African Socialist International
- APSP Website
- Dead Prez Lets Get Free, a Dead Prez album featuring recordings of Omali Yeshitela.
- International People's Democratic Uhuru Movement
- Uhuru Africa Club
- Uhuru Movement
- Burning Spear Uhuru Publications