After this decisive defeat, the UPGA prepared for the November 1965 legislative election in the Western Region in an attempt to gain control of the three southern regions and the Federal Territory of Lagos, the region surrounding the capital. If successful, the NPC-dominated NNA still would have controlled the House of Representatives, but it would have given the predominantly southern UPGA a majority in the Senate, whose members were chosen by the regional legislatures.

Once more NCNC strategy failed. Amid widespread charges of voting irregularities, Akintola's NNDP, supported by its NPC ally, scored an impressive victory in November. There were extensive protests, including considerable grumbling among senior army officials, at the apparent perversion of the democratic process. In the six months after the election, an estimated 2,000 people died in violence that erupted in the Western Region. In the face of the disorders, the beleaguered Balewa delegated extraordinary powers to the regional governments to deal with the situation. By this time, Azikiwe and the prime minister were scarcely on speaking terms, and there were suggestions that Nigeria's armed forces should restore order.

In January 1966, army officers attempted to seize power. In a well-coordinated action, the conspirators, most of whom were Igbo, assassinated Balewa in Lagos, Akintola in Ibadan, and Bello in Kaduna, as well as senior officers of northern origin. In a public proclamation, the coup leaders pledged to establish a strong and efficient government committed to a progressive program and eventually to new elections. They vowed to stamp out corruption and to suppress violence. Despite the bloody and calculated character of the coup, these sentiments appealed directly to younger, educated Nigerians in all parts of the country.

The army's commander in chief, Major General Johnson Aguiyi Ironsi, quickly intervened to restore discipline within the army. In the absence of Azikiwe, who was undergoing treatment in a London hospital, Balewa's shaken cabinet resigned, leaving the reins of authority to the armed forces. Ironsi, also an Igbo, suspended the constitution, dissolved all legislative bodies, banned political parties, and as an interim measure formed a Federal Military Government (FMG) to prepare the country for a return to civilian rule at an unspecified date. He appointed military governors in each region and assigned officers to ministerial positions, instructing them to implement sweeping institutional reforms.

Ironsi and his advisers favored a unitary form of government, which they thought would eliminate the intransigent regionalism that had been the stumbling block to political and economic progress. A decree issued in March abolished the federation and unified the federal and regional civil services. Civilian experts, largely Igbo, set to work on a new constitution that would provide for a centralized unitary government such as the NCNC had favored since the 1950s.

Although the decree contained a number of concessions to regional interests, including protection of northerners from southern competition in the civil service, Ironsi's action showed dangerous disregard for the nuances of regional politics and badly misjudged the intensity of ethnic sensitivities in the aftermath of the bloody coup. The failure of the military government to prosecute Igbo officers responsible for murdering northern leaders stirred animosities further. Igbo civil servants and merchants residing in the north made the situation even worse through their triumphant support for the coup. Furthermore, Ironsi was vulnerable to accusations of favoritism toward the Igbo. The coup was perceived not so much as an effort to impose a unitary government as a plot by the Igbo to dominate Nigeria. Likewise, many Muslims saw the military decrees as Christian inspired attempts to undermine emirate government.