[18] He conceived and acted in street plays and won prizes in national college festivals such as Mood Indigo (IIT Bombay), OASIS (Birla Institute of Technology and Science, Pilani) and St. Bedes Shimla.

[27] Apart from hosting the second season of MTV Rock On and India's Got Talent on Colors, he was also a part of the anchoring team of Extra Innings T20 for Indian Premier League Season 3 on SET Max with Gaurav Kapur, Samir Kochhar, and Angad Bedi,[28][29] following which he took up the offer of anchoring the dance-based reality show Just Dance on STAR Plus.

Khurrana made his acting debut in 2012 with Shoojit Sircar's romantic comedy Vicky Donor, co-starring Annu Kapoor and debutante Yami Gautam.

Marking the production debut of actor John Abraham, who cameoed in a promotional song, it starred Khurrana in the titular role of a sperm donor.

[31] Praising the film's ensemble cast, Sukanya Verma of Rediff.com wrote that Khurrana's "candid disposition and roguish face ensures his street smart drollery works like a breeze".

[38] Writing for The New York Times, Andy Webster disliked the film's "strained, contrived humor" but commended Khurrana for "holding his own opposite [Rishi] Kapoor".

[42] Khurrana's career prospects improved when he starred opposite newcomer Bhumi Pednekar in Sharat Katariya's romance Dum Laga Ke Haisha (2015).

[48] Saibal Chatterjee of NDTV wrote that Khurrana does a "convincing job of mutating from a brooding jilted lover to a crooked manipulator who puts his own interests above everyone else's".

[50] Rajeev Masand took note of how well the film handled sexuality without being crude and commended him for "investing the fellow with genuine likeability and an understated charm".

[53] His first role was in Sriram Raghavan's Andhadhun, a thriller co-starring Tabu and Radhika Apte, in which he played a blind pianist who unwillingly becomes embroiled in a murder.

[57][58] Andhadhun earned ₹4.56 billion (US$53 million) worldwide, a majority of which came from the Chinese box office, to become Khurrana's highest-grossing release and one of Indian cinema's biggest grossers.

[53][59] He next starred in Badhaai Ho, a comedy from director Amit Ravindernath Sharma about a young man whose middle-aged mother gets pregnant.

Anna M. M. Vetticad of Firstpost considered his performance to be "completely convincing" and commended him for choosing "to work in small films where the star is the story".

Highlighting caste discrimination in India, the film was inspired by multiple events including the 2014 Badaun gang rape allegations and the 2016 Una flogging incident.

[68] Writing for The Guardian, Wendy Ide commended him for "combin[ing] soulful Bollywood heartthrob charisma with an arrestingly intense performance.

"[69] Dream Girl starred him as a cross-gender actor who speaks in a female voice while working at a call centre which unwittingly attracts male attention.

[72] Rajeev Masand opined that Khurrana "cuts a sympathetic figure as another not-instantly-likeable loser" and added that he had "cornered the market when it comes to playing flawed, insecure men with confidence issues".

He found it in Shubh Mangal Zyada Saavdhan (2020), in which he played a gay man who has trouble convincing his partner's family of their relationship.

[83] Pallabi Dey Puryakastha of The Times of India noted that Khurrana's "body language tellingly portrays sadness and bitterness borne out of poverty".

[84] In 2021, Khurrana played a bodybuilder who falls in love with a trans woman in Abhishek Kapoor's romantic comedy Chandigarh Kare Aashiqui.

[86][87] Khurrana next headlined Anubhuti Kashyap's medical drama, Doctor G (2022), with Rakul Preet Singh and Shefali Shah, and starred in Aanand L. Rai's production, An Action Hero, directed by Anirudh Iyer.