Before making his debut as an actor, Rana entered the film industry as a producer with the movie Bommalata in 2004. The movie won the National Film Award for Best Feature Film in Telugu at the 53rd National Film Awards. He was next associated with the movie Sainikudu (2006) as a Visual effects coordinator, and won the Nandi Award for Best Special Effects.
It was in the year 2010 that Rana made his acting debut with the smash hit Telugu movie Leader, portraying the role of a young CEO of a US-based company. He was widely appreciated for his performance in the movie with The Times of India stating: Another lineage star Rana Daggubati takes his first bow at the Box Office with an inspiring political saga, he puts in a surprisingly mature performance (for a debutant) and shines in his role of a savvy young CEO of an US-based company who turns a conniving politician with effortless ease. Following his success in the debut movie, Rana then made his Bollywood debut with the movie Dum Maaro Dum directed in by Rohan Sippy in 2011. He once again impressed the audience and critics alike with his dashing performance. The Times of India dubbed it as a “dashing debut”.
In his third movie, the Telugu film titled Nenu Naa Rakhshasi (2011), Rana essayed the character of a professional killer. However, unlike his previous movies, the movie proved to be a box office disaster. The actor’s next two releases received mixed response commercial and critical response. The first being Naa Ishtum (2012), a Telugu movie directed by Prakash Toleti, and the second being a Hindi movie, Department, directed by Ram Gopal Varma. Rana’s next Telugu movie, Krishnam Vande Jagadgurum, directed by Krish, proved to be box office hit and he also went on to make his Tamil film debut with Arrambam (2013).
The year 2013 turned out to be one of the most important years of Rana’s acting career. He signed two movies that year, which later went on to become landmarks in Telugu Cinema viz. Baahubali: The Beginning and Rudramadevi; both these movies released in 2015.
Baahubali: The Beginning, an epic historical movie directed by S.S. Rajamouli features Prabhas, Tamannaah Bhatia, and Anushka Shetty in lead roles. The movie went on to become the highest grossing Indian film within India and the highest grossing Telugu film of all time. Rana played the role of the antagonist Bhallala Deva, and was praised for his performance with critic Archita Kashyap stating: Be it the war sequences, or sword fighting; or a visual spectacle, or pure entertainment it is worth a watch. Kudos to the dedication of S S Rajamouli and his leading men, Prabhas & Rana, for spending years putting this film together. Actually, in its imagination & Indianness, Baahubali might just be a whole new start.” Three months after Baahubali was released, Rana’s next movie Rudhramadevi, a 3-D historical movie based on life of the ruler Rudrama Devi (died 1295), directed by Gunasekhar, hit the theaters. The movie opened to positive reviews and grossed INR 32 crores at the box office. Rudhramadevi was also shortlisted for the Academy Award for Best Foreign Language Film.
In 2016 he was seen in the movie Bangalore Naatkal, which features an ensemble cast that includes Arya, Sri Divya, Bobby Simha, Raai Laxmi, Parvathy, and Samantha Ruth Prabhu. The movie, directed by Anjali Menon, received mixed response at the box office. However, his much-awaited 2017 release Baahubali 2: The Conclusion has constantly been in news for most of 2016. Apart from Baahubali, his other releases for 2017 include the bilingual movie The Ghazi Attack, which is made in Telugu and Tamil, Nene Raju Nene Mantri, and another bilingual movie titled Madai Thiranthu in Tamil and 1945 in Telugu.