In 1578 Oda Nobunaga called on his retainers to attack the Mori clan. Nagaharu almost decided to lead the Oda troops, but after hearing that the low-born general Hashiba Hideyoshi, whom he did not respect, was allied with the Oda faction he revolted, instead allying himself with Hatano Hideharu of Tamba province.
This led to Nagaharu being besieged by Hideyoshi's troops on the orders of Nobunaga. Nagaharu took a stand in Miki Castle, starting the Siege of Miki. The siege did not go well for Hideyoshi, and with a revolt by Araki Murashige and the help of the Mōri clan Nagaharu successfully repelled the Oda force. But Hideyoshi returned and this time instead of launching a direct assault, he launched multiple sieges against smaller castles like Kamiyoshi Castle and Sigata Castle to cut off the support from Mori. This led to a rapid depletion of food, and in 1580, with no hope of another reinforcement from Mōri clan, Nagaharu committed seppuku in exchange for the lives of the troops in Miki Castle.