Usha Sami was born in a Tamil brahmin family that hailed from Tamil Nadu, in Madras (now Chennai) in 1947. Her father Sami Iyer, later became the police commissioner of Bombay. She has three sisters Uma Pocha, Indira Srinivasan and Maya Sami, all of whom are singers and two brothers, one of whom is named Shyam. She was the fifth of six children. As a child, she lived in the police quarters at Lovelane in Byculla in Bombay and attended a local school.
When she was in school she was thrown out of music class because she didn't fit in with a voice like hers. But her music teacher recognized that she had some music in her that would give her clappers or triangles to play. Even though she was not formally trained in music, she grew up in an atmosphere of music. Her parents used to listen to a wide range from Western classical to Hindustani and Carnatic including Kishori Amonkar and Bade Ghulam Ali Khan on radio and she used to join them. She used to enjoy listening to Radio Ceylon.
Her next door neighbour was S.M.A. Pathan, who was then the deputy commissioner of police. His daughter, Jamila, inspired Usha to learn Hindi, wear salwar kameez and take up Indian classical music. This fusion approach helped her to pioneer her unique brand of Indian pop in the 70s. She is married to Jani Chacko Uthup who is originally of Kerala extraction since 1971. They have a daughter Anjali and a son Sunny. She currently lives in Calcutta with her husband. She is considered an icon of modern Kolkatta and is an active social presence in the city life.