Sameera’s father Chinta Poli (C.P.) Reddy is a businessman, and her mother Nakshatra, referred to as Niki by her daughters and in the media, was a microbiologist and worked with an NGO. She has two siblings, Meghna Reddy, a former VJ and supermodel and Sushma Reddy, a Bollywood actress and model, both elder to her. She did her schooling at Bombay Scottish School in Mahim,Mumbai and graduated from Sydenham College. Reddy got married to Akshai Varde an entrepreneur on 21 January 2014. It was a traditional Maharashtrian wedding. They welcomed their son on 24 May 2015.
Sameera made her debut as an actress in Saravana Subbiah's Tamil film, Citizen, during late 2000, but eventually did not feature. She caught the attention of Bollywood and was cast in a pivotal role in the 2002 Hindi film Maine Dil Tujhko Diya. In 2004, she appeared in Musafir. Reddy appeared in the Tamil film Vaaranam Aayiram directed by Gautham Menon, which was a blockbuster. She was signed for two films of Gautham Menon, Yohan Adhyayam Ondru and Dhruva Natchathiram. They were eventually dropped. Her future projects are Bemisaal, The Migration, Bhale Tammudu.