After starting her career on television, Neethu, primarily a Kannada film actress, made her feature film debut in 2004 with the horror movie Yahoo. Although that movie was an average grosser, she was seen in two other movies that year - Jennifer and Joke Falls. It was after Joke Falls that she received recognition and bagged the lead role in Beru, which went on to win the National Film Award for Best Feature Film in Kannada. Making her Malayalam debut, Neethu starred alongside Mohanlal in the 2006 drama Photograph.

The following year, in 2007, she made her Tulu movie debut with the movie Koti Chennaya, which won the National Film Awards Best Feature Film in Tulu and her performance in the movie won her the Karnataka State Film Award for Best Supporting Actress. Her next project, Gaalipata, won her widespread acclaim, with her receiving two Best Supporting Actress nominations, one at Filmfare and the other at Suvarna Film Awards. Some of her projects include Manasaare, Aithalakkadi, and Ujwadu.

In 2014, the actress was seen in the television reality show Bigg Boss Kannada in its second installment. After her eviction from the show, she was seen making several special appearances in movies such as Fair & Lovely, Jaggi, Abhinetri, and Ring Road. Her other projects include Sithara, 1888, and Vajramukhi.