Born in 1545 into the Azai family of Ōmi Province, he inherited the family headship from his father Hisamasa and ruled northern Ōmi. In 1567 he entered into a strategic marriage with Oda Nobunaga's sister Oichi, forming an alliance with the Oda. In 1570, when Nobunaga attacked their mutual ally Asakura Yoshikage, Nagamasa broke the Oda alliance to honour his old bond with the Asakura and struck at Nobunaga from the rear (the Battle of Anegawa; the retreat from Kanegasaki). But he was defeated at the Battle of Anegawa by the combined Oda-Tokugawa forces, and thereafter the Azai were reduced to straits. In 1573 Nobunaga's large army surrounded and took Odani Castle, and Nagamasa took his own life. He was 29. He is praised by later generations as a warrior who valued loyalty and did not betray his old alliance, yet he is also a tragic figure whose choice led to his family's destruction. With his wife Oichi he fathered the three sisters Chacha (Lady Yodo), Hatsu, and Gō.

A sincere warrior who valued duty and integrity above all else. The essence of Nagamasa is revealed in his honouring of the alliance with the Asakura that his father Hisamasa had concluded, beyond mere calculations of self-interest. The dissolution of the Oda alliance was a decision that staked the family's survival, but the strength of will and sincerity he showed in carrying it through moved many people. He also showed bold decisiveness in inheriting the family headship young and forcing his father into retirement, yet he prioritised spiritual integrity over political realism.

He is counted as one of the representative figures of the Sengoku period as a tragic warrior who valued loyalty. The three sisters he fathered with Oichi (Chacha, Hatsu, and Gō) left great footprints in subsequent Sengoku history, with Chacha in particular becoming deeply involved in the Toyotomi regime as Lady Yodo. The ruins of Odani Castle (Nagahama City, Shiga Prefecture) survive today as a historic site representing mountain castles of the Sengoku period. The history of three generations of the Azai (Sukemasa, Hisamasa, Nagamasa) is deeply etched in the regional history of northern Shiga Prefecture.