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Born the daughter of Saito Toshimitsu, a warrior of Mino Province. Because her father, a senior retainer of Akechi Mitsuhide, was executed after the Honnoji Incident, she grew up in difficult circumstances. In 1604 she applied for the position of Tokugawa wet nurse and was selected to nurse the third shogun Tokugawa Iemitsu. While Iemitsu's parents, Hidetada and O-e (the Lady Ogo), showed favoritism toward his younger brother Tadanaga and considered disinheriting Iemitsu, Kasuga steadfastly supported him. In 1629 she traveled to Kyoto on her own initiative to negotiate with the imperial court, obtained an audience with Emperor Go-Mizunoo, and received the imperial sanction to be invested as Junior Third Rank. This act led to her separation from her husband Inaba Masanari, but by invoking imperial authority she secured her position within the shogunate. She made major contributions to formalizing the Ooku (inner palace) system and laid the foundations of its later form. She died in 1643 at age 65, and it is said that Iemitsu grieved deeply.

Possessed of strong will and political insight, she was bold enough to defy convention and even the orders of her lord when it served her purpose. Deep affection and loyalty to Iemitsu drove her actions, and as his protector she commanded the respect of all within the shogunate. Highly capable in practical matters, she was also an outstanding organizer who managed the complex institution of the Ooku.

She is remembered in history as the person who laid the foundations of the Ooku institution. She contributed to establishing the authority of Shogun Iemitsu and played a role in the stable political structure of the Edo period. Her unilateral initiative in negotiating with the imperial court is also valued as a rare case of a woman intervening in the formal political sphere. Kasuga no Tsubone continues to be depicted in many works including NHK historical dramas and films.