From there, Nobunaga continued his expansion, sending Akechi Mitsuhide to pacify Tanba Province and Hashiba Hideyoshi to Himeji Castle, before advancing upon the Mori clan in Nagato Province. The end of the Takeda clan came in 1582, when Oda-Tokugawa forces conquered Kai Province. Takeda Katsuyori was defeated at the Battle of Tenmokuzan and then committed seppuku.
By 1582, Nobunaga was at the height of his power and, as the most powerful warlord, the de facto leader of Japan. Nobunaga and Ieyasu finally defeated the Takeda at the Battle of Tenmokuzan, destroying the clan and resulting in Takeda Katsuyori fleeing from the battle before committing suicide with his wife while being pursued by Oda forces. By this point, Nobunaga was preparing to launch invasions into Echigo Province and Shikoku. Nobunaga's former sandal bearer, Hashiba Hideyoshi, invaded Bitchū Province and laid siege to Takamatsu Castle. The castle was vital to the Mori clan, and losing it would have left the Mori's home domain vulnerable. Mori reinforcements led by Mōri Terumoto arrived to relieve the siege, prompting Hideyoshi to ask for reinforcements from Nobunaga, who promptly ordered his leading generals to prepare their armies, with the overall expedition to be led by Nobunaga. Nobunaga left Azuchi Castle for Honnō-ji, a temple in Kyoto he frequented when visiting the city, where he was to hold a tea ceremony. Hence, Nobunaga only had 30 pages with him, while his son Oda Nobutada had brought 2000 of his cavalrymen.
Akechi Mitsuhide, stationed in the Chūgoku region, decided to assassinate Nobunaga for unknown reasons, and the cause of his betrayal is controversial. Mitsuhide, aware that Nobunaga was nearby and unprotected for his tea ceremony, saw an opportunity to act. Mitsuhide led his army toward Kyoto under the pretense of following the order of Nobunaga, but as they were crossing Katsura River, Mitsuhide announced to his troops that "The enemy awaits at Honnō-ji!" (敵は本能寺にあり, Teki wa Honnō-ji ni ari). On 21 June 1582, before dawn, the Akechi army surrounded the Honnō-ji temple with Nobunaga present, while another unit of Akechi troops were sent to Myōkaku-ji in a coup. Although Nobunaga and his servants resisted the unexpected intrusion, they were soon overwhelmed. As the Akechi troops closed in, Nobunaga decided to commit seppuku in one of the inner rooms. Reportedly his last words were, "Ran, don't let them come in…" referring to his young page, Mori Ranmaru, who set the temple on fire as Nobunaga requested so that no one would be able to get his decapitated head. Ranmaru then followed his lord, with his loyalty and devotion makes him a revered figure in Japanese history. Nobunaga's remains were never found, a fact often speculated about by writers and historians. After capturing Honnō-ji, Mitsuhide attacked Nobutada, eldest son and heir of Nobunaga, who also committed suicide.