Sudeep met Priya Radhakrishna in Bengaluru, in 2000 and they married in 2001. Priya worked in an airline company and then in a bank, prior to their marriage. Their only child, Saanvi, was born in 2004. In 2013, Sudeep launched Stage 360°, an events management company, that his wife took an active part in. The couple split in September 2015, and reconciled

Sudeep began his film career in Thayavva (1997). He then played a supporting role in Prathyartha, directed by Sunil Kumar Desai, and a lead role in the same director’s Sparsha. In 2001, a role in Huchcha gave him his first big following. In 2008 he made his Bollywood debut in Phoonk. He has also starred in Ram Gopal Varma’s movies Rann, Phoonk 2 and Rakta Charitra. They were followed by Kempe Gowda and Vishnuvardhana (2011).

Sudeep made his debut in Telugu cinema in 2012, with S. S. Rajamouli’s Eega, a fantasy film in which he portrayed an industrialist who, on falling for an NGO worker (played by Samantha Ruth Prabhu), kills her alleged lover, who begins to haunt him in the form of a housefly. The film and Sudeep’s performance were highly acclaimed. In 2013, Bachchan and Varadanayaka were released. His next film was a drama titled Maanikya that he also directed, a remake of the Telugu film, Mirchi (2013). In 2015 he starred in Ranna, a remake of the Telugu film, Attarintiki Daredi, and played a cameo role as a Persian arms trader in Baahubali: The Beginning, directed by S. S. Rajamouli—the year’s highest-grossing film.

Sudeep has been described by the critics as one of the most talented actors in Kannada cinema. He was listed first in the Times 25 Most Desirable Men in Bangalore in 2012. In 2012, he was given a title, “Abhinaya Chakravarthy”, by a Kannada organisation, Karnataka Rakshana Vedike.

In 2012, Sudeep was signed as the Brand Ambassador of Joyalukkas, a Jewellery Retail Chain. In 2013, he was appointed as the Brand Ambassador for Bangalore Traffic Police Department and Income Tax Department. In 2014, he was appointed as the Brand Ambassador for Intex Technologies (India) Mobiles & Paragon Footwear.

In 2013, on World AIDS Day, Sudeep teamed up with Vijay Raghavendra and other actors to record voiceovers for the TeachAIDS interactive software, developed at Stanford University.

Sudeep made his TV debut in the serial Premada Kadambari, named after a line in the song Bandhana on Udaya TV. He was roped in to play the main host of the reality show Pyate Hudgeer-Halli Lifu, aired on Suvarna, which was an immediate success. Endemol Shine Group’s flagship show Big Brother was adapted to Kannada as Bigg Boss Kannada and Sudeep was the chosen to play the host for the first season which was aired on ETV Kannada. He continued to host the second season on Asianet Suvarna. Colors Kannada (formerly ETV Kannada) regained the rights to the show in 2015 with Sudeep signing a five-season deal to host the show which was estimated to be around ₹20 crore (equivalent to ₹24 crore or US$3.4 million in 2019) which was a landmark deal in Kannada television industry.

In 2015, Sudeep appeared in advertisements in the Kannada language for OLX.in, along with the veteran Kannada actor, Anant Nag. He had previously appeared in ads with Sadhu Kokila for the same company.

In 2019, Sudeep was seen in the Hindi film Dabangg 3 where he played the archenemy of Salman Khan’s Chulbul Pandey.