Karthika was born to former Indian actress Radha, and is the niece of actress Ambika. She has two siblings, a brother and a sister, Thulasi Nair, who is also a South Indian actress. She did her schooling in Podar International School in Mumbai and studied for an international degree in Business from college affiliated to London School of Economics.
She made her acting debut at the age of 17 in the 2009 Telugu film, Josh opposite Naga Chaitanya. Though the film received mixed reviews, her performance as Vidya, an elementary school teacher desperate to attend college is received well. She received Santosham Film Award for Best Debut Actress. Her second movie was in Tamil called Ko directed by famous film director K. V. Anand, pairing with Jiiva which did very well at the box office. The film received cult status in the genre of political thrillers. Her performance as Renuka Narayanan, an investigative journalist, who exposes the blunders of politicians was hugely applauded. She received nomination for Siima for Best Actress – Tamil at 1st South Indian International Movie Awards. She then appeared in the Malayalam film, Makaramanju directed by Lenin Rajeendran, starring alongside ace cinematographer and director Santosh Sivan. She donned a dual role, one of a painting model, Sugandha Bai and Urvashi, the Celestial beauty. Her first ever dual role was well received and critics raved her performance. British director Danny Boyle was highly impressed with her work in the film. She received Siima for Best Debut Actress – Malayalam at 1st SIIMA Awards and Kerala Film Critics Association Award for best debut actress.
In 2012, she appeared in a single Telugu film, Dammu directed by Boyapati Srinu, in a limited glamorous role. Her performance and the movie received negative reviews and ended up to be a commercial failure. She was paired with N. T. Rama Rao Jr. and shared screen space with Trisha.
In 2013, she appeared in the comedy film,Proprietors: Kammath & Kammath alongside veteran actors Mammootty and Dileep .Her performance as Surekha,a Christian mute young widow who works in Indian Revenue Service was well received and so is the film.Later she appeared in the titular role in the Tamil film,Annakodi directed by legendary filmmaker P. Bharathiraja.Though the film received negative reviews, her performance as a damsel in distress received positive response.She made her Kannada debut with Brindavana,a remake of Telugu blockbuster Brindavanam. The film repeated the success of the original.In the film she was paired with Darshan.
In 2014, she appeared in her third Telugu film, Brother of Bommali, where she played Lucky, tomboy twin sister of Allari Naresh's character. The film starred top comedians like Brahmanandam, Ali and villains like Kelly Dorji, Nagineedu and Vineet Kumar. In the film she has donned a full length comic role. Her performance received high critical acclaim and received her first ever Filmfare nomination in the category of Filmfare Award for Best Supporting Actress -Telugu at 62nd Filmfare Awards South.
In 2015, she appeared in her third Tamil Political crime drama film, Purampokku Engira Podhuvudamai, directed by National Film Award winner S. P. Jananathan alongside Arya, Vijay Sethupathi and Shaam. Her performance as Kuyili, a mastermind behind a prison break plan received positive response. The film received commercial success and critical acclaim.
Her much delayed film Vaa Deal, starring Arun Vijay is yet to be released.
In the year 2017, Nair made her Television debut with Epic drama, Aarambh written by K. V. Vijayendra Prasad and directed by Goldie Behl which aired on Star Plus, starring opposite Rajneesh Duggal. In the series, she played the role of Devasena, a warrior queen, which was well received by both audience and critics. The show aired its last on 10 September 2017.The show went off air due to low TRPs,while netizens watched the show religiously online.The role of Devasena is considered one of the best and strongest characters of Indian Television.She gained huge following and appreciation among Television audience.FilmsTelevision2009: Santosham Film Award for Best Debut Heroine – Josh2011: Kerala State Film Critics Award for the Best Début – Makaramanju2011: Vanitha Film Award for Best Début – Makaramanju2011: SIIMA Award for the Best Female Debut – Malayalam – Makaramanju2011: Jaya TV Award for the Sensational Debut Heroine – Ko'
2011: Nominated – SIIMA Award for the Best Female Debut – Tamil – Ko
2015: Nominated – Filmfare Award for the Best Supporting Actress – Telugu – Brother of Bommali