Eboe-Osuji was called to the Nigerian Bar in 1986 and practised briefly there. After obtaining his master of laws degree from McGill in 1991, he worked as a barrister in Canada, having been called to the Bar in Ontario and in British Columbia in 1993. From 1997 to 2005, Eboe-Osuji worked at the International Criminal Tribunal for Rwanda as prosecution counsel and senior legal officer to the judges of the tribunal. From 2005 to 2007, he worked in Canada as a barrister and law lecturer. Working for the Special Court for Sierra Leone as senior prosecution appeals counsel in 2007/08 and returning to the ICTR from 2008 to 2010 as Head of Chambers, he became the Legal Advisor to the United Nations High Commissioner for Human RightsNavi Pillay in 2010, and held a cross-appointment as the principal prosecution appeals counsel at the Special Court for Sierra Leone, in the case of Charles Taylor, the former President of Liberia. He has authored two books and numerous law journal articles in international law.
On 16 December 2011, Eboe-Osuji was elected as a judge of the InternationalCriminal Court. He won the office in the fifteenth ballot in the Assembly of States Parties. He took office on 11 March 2012. From September 2013, Eboe-Osuji – alongside Judges Olga Venecia Herrera Carbuccia and Robert Fremr – presided over the trial against Deputy PresidentWilliam Ruto of Kenya, who was accused of stoking a wave of killing for political gain after the country's contested 2007 elections. Early on, he warned Kenyan media and bloggers that anyone revealing the identity of a protected witness at the Ruto trial could be guilty of contempt of court; ICC chief prosecutorFatou Bensouda had previously complained that some witnesses were being intimidated in Kenya, some of whom withdrew from the case. Following Eboe-Osuji's own request, the Presidency of the ICC decided to reconstitute Trial Chamber V in the trial against Uhuru Muigai Kenyatta and replace him with Judge Geoffrey Henderson in early 2014. However, Eboe-Osuji remains the Presiding Judge in Trial Chamber V which continues to hear the case against Ruto and former Kass FM broadcaster Joshua Sang. In April 2014, his chamber issued subpoenas for several prosecution witnesses no longer willing to testify in the case. Shortly after, Eboe-Osuji told off the government of Kenya for turning to the principle of sovereignty "at every convenient opportunity, with the evident aim of frightening judges".