Born in the town of Mbale in eastern Uganda, Onyango-Obbo studied at Makerere University in Kampala, and the American University in Cairo where he obtained a Masters degree in journalism. In 1991, he was a Nieman Fellow at Harvard University.
On May 1999, during the Second Congo War, Onyango-Obbo and other editors of The Monitor – Wafula Ogutu and David Ouma Balikowa – were arrested and charged with "sedition" and "publication of false news"´, following the publication of a photograph of a naked woman being sexually abused by men in military uniform. Ugandan officials insisted that the assailants might be soldiers from Congo or Zimbabwe (who where also involved in the Congo war), and could not possibly be Ugandan soldiers as the photo caption claimed. Onyango-Obbo and the other editors were acquitted on 6 March 2001.