The research examines Nigerian newspapers’ framing of the Biafra Agitation under President Muhammadu Buhari’s administration with a content analysis of the Leadership, Daily Trust, the Punch, and Daily Sun Newspapers. The predominant frames in all the contents were protest/ freedom frame, ethnic frame and religion frame among others. The research is anchored on the Media Framing Theory and Agenda Setting Theory which are twin brother theories. The duo theories gave the research more depth and relate it to the existing body of knowledge. Content analysis as a quantitative research method coupled with coding book, 9 content categories including the 10 frames under the framing category were used. Also, 142 stories were analyzed from the selected papers which was analysed using frequency and percentage table method. Findings shows that the Southern papers has more stories related to Biafra agitation for secession more than it was found in the Northern newspapers. Framed stories on Biafra agitation were given prominence within that period as many of the stories were not only illustrated but also used colour photo coupled with reasonable proportion of space were given in the newspapers to cover Biafra Agitation because it is a serious issue threatening the national unity. It is recommended that the media and other owners should shun politics while dealing with issue of national interest and be conscious in the content since the ‘medium is the message’ to prevent collapse of national interest.