Ujitsuna was the second Hôjô daimyô and was the eldest son of Hôjô Soun (1432-1519), who was known in life as Ise Shinkuro or Sozui. He assumed formal leadership of the family with the death of his father in 1519.
By the time Ujitsuna had become daimyô, the Hôjô controlled Izu Province, most of Sagami Province, and was starting to exert some influence in Musashi. Ujitsuna moved the center of clan leadership to Odawara Castle in Sagami Province. He then adopted the name Hôjô, presumably for the prestige value. Soun is often described as assuming that name but no evidence exists to support that claim. In any event, 1523 is when the name Hôjô first appears in records.
Ujitsuna carried on his father's ambitions, pushing forward the Hôjô borders whenever the opportunity presented itself. In 1524 he went to war with the Ogigayatsu-Uesugi and took Edo Castle in Musashi Province, which he gave to Toyama Tadakage. He ordered repairs to Kôzuke Castle (at present-day Yokohama) and consolidated his hold in southern Musashi. The Satomi of Awa Province staged a naval landing at Kamakura and in the course of the fighting that resulted much of the town was burned, including the famous Tsurugaoka Hachiman Shrine. The Satomi withdrew but a feud had been joined that would last for many decades. Afterwards, the Moro and Okamoto families of Musashi, vassals of the Uesugi, secretly went over to Ujitsuna. Thus assured, Ujitsuna pushed northward into the province. The Ogigayatsu resisted stubbornly and the Hôjô expansion was by no means rapid.
In the wake of the Satomi attack on Kamakura, Ujitsuna took up the task of rebuilding the Tsurugaoka Hachiman Shrine. The court recognized Ujitsuna' efforts by awarding him the title of sakyô dayu and the Fifth Court Rank, Junior Grade. An Imperial messenger arrived in 1533 ordering Ujitsuna to pay the annual tribute from Izu Province to the Court. This in effect legitamized the Hôjô's rule of Izu Province and Hôjô control of Sagami was implied as well.
In 1535, Ujitsuna marched out to support his ally Imagawa Ujiteru. In his absence the Ogasawara-Uesugi struck Sagami Province, causing damage to Oiso, Hiratsuka, Ichinomiya, Kowade, and Kagenuma. Ujitsuna sped back to Sagami and made a call to sympathetic but previously uncommitted warrior families in Musashi, Kazusa, and Awa to support him. A number of these houses responded, goaded on by an abiding resentment of the often heavy-handed rule of the Uesugi. Reinforced, Ujitsuna met the Uesugi army at the Irumagawa and defeated it.
Ogagiyatsu-Uesugi Tomooki died in 1537, prompting Kaigen Sôzu of the Tsurugaoka Hachiman shrine to record that the people of Sagami Province 'rejoiced in the belief that now the land would be at peace.' As it happened, Tomooki's heir, Tomosada, proved just as willing to carry on the war with the upstart Hôjô. Ujitsuna struck out, taking Kawagoe Castle in Musashi and forcing Tomosada to take up at Matsuyama Castle. The Satomi of Awa, who had presently been recovering from a succession dispute, now allied with Ashikaga Yoshiaki, the koga kuboi. When Ujitsuna became preoccupied with a dispute with the Imagawa, Satomi Yoshitaka (1512-1574) joined forces with Yoshiaki and invaded the Hôjô domain in 1538. Ujitsuna hastily raised troops from Sagami and Izu. He combined his forces at Edo and then pushed on to meet the allies at Konodai. The result was a decisive victory for Ujitsuna. Yoshiaki was killed and the Satomi in total retreat.
The year following Konodai, Ujitsuna went to war with the Imagawa and seized land west of the Fuji River. Over the course of twenty years, Ujitsuna had slowly but methodically expanded the Hôjô domain and proven himself a capable general. Like his father, Soun, Ujitsuna worked to secure the respect of the people through generous donations to temples and in the application of reasonable tax rates. In addition to repairing the Tsurugaoka Hachiman Shrine, Ujitsuna also ordered repairs carried out on the Samukawa Shrine, the Hokane Gangen, Rokusho Myô at Kôzu, and the Izu Mishima Shrine. He went on to grant tax and labor exemptions to other shrines. Finally, he built a temple, the Soun-ji, in honor of his father, an act that garnered him praise from within and without the Hôjô domain.
Ujitsuna was succeeded by his eldest son, Ujiyasu. He had earlier adopted a son from the Kushima family of Suruga Province. The boy became Hôjô Tsunanari, destined to be a valued retainer for Ujiyasu.