For the first time in over two decades, diphtheria outbreak was confirmed and responded to in Nigeria. Findings from the investigation suggests sub-optimal vaccination coverage for diphtheria as the main driver of the outbreak. We strengthened laboratory capacity for confirmation, improved access to diphtheria anti-toxin, conducted reactive vaccination and sensitized clinicians and community members. We recommended strengthening routine immunization, and formulation of diphtheria booster dose policies in Nigeria.