The organisation was founded by Mary Lawlor, former director of the Irish Section of Amnesty International with a US$3 million donation from businessman and philanthropist Denis O'Brien.

Front Line Defenders has Special Consultative Status with the United Nations Economic and Social Council, and has Observer Status with the African Commission on Human and Peoples' Rights.

In 2006 Front Line Defenders established a European Union office in Brussels.

In October 2021, Front Line Defenders found evidence that various Palestinian citizens belonging to human rights groups which had been outlawed by Israel, had been targeted by spyware made by the Israeli technology company, NSO Group.

[1][2] In 2005 this award was established, which according to the organisations website is awarded to a human rights defender "who through non-violent work, is courageously making an outstanding contribution to the promotion and protection of the human rights of others, often at great personal risk to themselves".