Nirupama was born in the Southern Indian town of Coimbatore. She started playing tennis at the age of 5 and was influenced very much by her brother. Her father K.S. Vaidyanathan was a cricketer who had played for Tamil Nadu in Ranji Cricket tournament coached her at the start of her career. Her first tennis tournament foray was the National Under 12 tournament, where she reached the semi-final and went on to win her 1st National title in Under 14 age group at the age of 13. One year later in 1991, she won the National Women's title at age 14. She won the National Women's title in 1992-1996.

In 1996, she moved to Luxembourg and she turned professional at the age of 18. Nirupama shifted her base to Sarasota, Florida in 1997 where she trained with David O Meara who was the former coach of Leander Paes for two years. In 1998 Australian Open, she became the first Indian woman in the modern era to feature and win a round at a main draw Grand Slam, beating Italy's Gloria Pizzichini. She has also won the Bronze Medal at the 1998 Bangkok Asian Games in Mixed Doubles, partnering Mahesh Bhupathi.

She retired during the later 2000s. She made a comeback in 2010 when she represented India to play in the Commonwealth Games 2010 and in Asian games in Guangzhou as a 33-year old.

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