Upendra Limaye was born on November 8, 1969, in Pune, Maharashtra, and grew up in the city's Sadashiv Peth area, attending Bharti Vidyapeeth and New English High School. He is married to Dr. Swati Limaye, with whom he has two children.

He has built an extensive career spanning experimental theatre, Marathi parallel cinema, television, and mainstream Hindi and South Indian films, collaborating with directors including Madhur Bhandarkar, Ram Gopal Varma, Amol Palekar, and Jabbar Patel. His performance in the Marathi film Jogwa (2009) earned him the National Film Award and Maharashtra State Film Award for Best Actor, making him the first Marathi actor honored with the National Award, and in 2013 Forbes included it among its "25 Greatest Acting Performances of Indian Cinema" for the centenary of Indian cinema. His other acclaimed credits include Mukta, Bangarwadi, Sarkarnama, Dhyasparva, Chandni Bar, Page 3, and Traffic Signal, alongside more recent mainstream roles in Antim: The Final Truth (2021) and Animal (2023). He appears in Romanchakam, a romantic comedy-thriller from Sandeep Reddy Vanga's production banner.