Masako was born Masako Odate in Shibuya, Tokyo, the only daughter of Sue and Kazu Odate. Raised in Naka-ku, Yokohama, while in junior college in 1976 she auditioned for the lead role in Nihon TV's drama Ai ga miemasu ka ("Can you see love?"). Chosen from 4,000 applicants, she dropped out of school to pursue an acting career, playing the part under her real name Masako Odate. Masako's mother initially objected to her choice of career and requested that she not use the Odate family name if she gained further work. In 1977, she changed her name to Natsume.
In 1977, she was chosen to represent Kanebo Cosmetics, achieving great popularity after appearing topless as the "Kooky Face" girl in an ad for sunscreen. This popularity led to her recording a song later that year called "Oh! Cookie Face." Many bit parts and a few leads in movies followed, but she continued in television.
In 1978-79, she played the male part of Tripitaka (Sanzō-hōshi, Japanese translation of Sanzang-fashi) in the 1970s Japanese TV program Saiyūki, which proved popular in many English-speaking countries in the 1980s, when dubbed by the BBC and titled Monkey. Masako won the part as she had matched contemporary descriptions of Sanzō-hōshi's appearance more closely than male actors who auditioned.

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