In 1561, Saitô Yoshitatsu, who had continued to fend off advances by the Oda, passed away, probably of leprosy. This left his son, Tatsuoki, in command and Nobunaga was quick to take advantage of the new lord's weak character. By bribing away key Saito generals, Nobunaga was able to weaken the defenses of Mino and in 1567 he attacked Inabayama, the headquarters of the Saitô clan. According to tradition, the hill-top castle was brought down by Hashiba (Toyotomi) Hideyoshi, although this valuable Oda retainer does not begin appearing in written records until around 1576.

The following year, Nobunaga moved his capital to Inabayama and renamed the castle Gifu. Everything about the move was auspicious, and made possible by two alliances - one to Matsudaira Motoyasu, and another to Takeda Shingen of Kai and Shinano. The name Gifu was taken from the castle from which Wu Wang, ruler of the Chou, had set out in the 12th Century to unify China. Emperor Ogimachi sent a letter of congratulations and Nobunaga adopted the motto Tenka Fubu, or 'the realm covered in military glory' (or, alternatively, 'The nation under one sword").

The only real opposition to his moves in Mino came from the Asai, who had declared war on the Saito at around the same time. Asai Nagamasa considered Mino at least partly his, and a small war quickly brewed up on the Ômi-Mino border. Nobunaga quickly arranged a peace and sealed an alliance by marrying his sister (O-ichi) off to Asai Nagamasa.

Nobunaga's ambition was given a powerful stimulant with the arrival of Ashikaga Yoshiaki at Gifu in 1567. The brother of the late shogun, Ashikaga Yoshiteru, murdered in 1565, Yoshiaki had spent the intervening years seeking out a patron. Yoshiteru's assassins - the Miyoshi and Matsunaga clans - had seen fit to legitimize their domination of Kyoto politics by naming the 2-year old Ashikaga Yoshihide as Yoshiteru's successor. When Yoshiaki heard the news, he gave up a Buddhist priesthood and fled with Hosokawa Fujitaka, both out of fear for his own life and in the hopes he would find a warlord strong enough to set things right in Kyôto. That he was the logical choice to follow Yoshiteru was clear…finding a Daimyô that would do something about it proved difficult. In his search, he approached the Takeda of Wakasa (not to be confused with the Takeda of Kai), the Uesugi of Echigo, and the Asakura of Echizen. The last seemed the most promising, in terms of military strength relative to a proximity to the capital, and indeed, Asakura Yoshikage promised to help. But Yoshikage stalled and in the end admitted that he was powerless to assist Yoshiaki's nomadic party.

Then Yoshiaki turned to Oda Nobunaga, who fairly jumped at the opportunity. In fact, he had expressed a desire in late 1565 to do just what Yoshiaki was asking, and it may be that Yoshiaki had been leery of approaching this young upstart to begin with. Uesugi and Asakura, after all, were names that carried quite a bit of prestige along with them. But, by 1567, Yoshiaki had evidently decided that beggars couldn't be choosers.

In 1568 Nobunaga's army marched westward in Yoshiaki's name, brushing aside the Rokkaku of southern Omi and putting to flight Miyoshi and Matsunaga. Matsunaga Hisahide promptly submitted (for which he was confirmed Daimyô of Yamato) while the Miyoshi withdrew to Settsu. In the ninth month Nobunaga entered Kyoto and within three weeks Yoshiaki was installed as the fifteenth Ashikaga shogun with the approval of Emperor Ogimachi. The mutually beneficial relationship of Yoshiaki and Nobunaga had thus far borne sweet fruit. In time, it would grow quite sour, foreshadowed by Nobunaga's refusal to accept the position of Kanrei, or deputy shogun, even when the Emperor himself requested he do so in 1569 . Nobunaga seemed determined to exist in a sort of political limbo, and expressed little interest in any orthodox rank or titles, including, as we shall see, that of shogun. That Nobunaga was the real ruler in Kyoto was the only part of the equation that lacked any sort of ambiguity.