Khurrana was born on 14 September 1984 in Chandigarh to Poonam and P. Khurrana, as Nishant Khurrana. His parents changed his name to Ayushmann Khurrana when he was 3 years old. He was a part of Guru Nanak Khalsa College. He studied at St. John’s High School, Chandigarh and DAV College, Chandigarh. He majored in English literature and has a master’s degree in Mass Communication from the School of Communication Studies, Panjab University. He did serious theatre for five years. He was also the founding member of DAV College’s “Aaghaaz” and “Manchtantra”, which are active theatre groups in Chandigarh. 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. He also won a Best Actor award for playing Ashwatthama in Dharamvir Bharati’s Andha Yug.

After completing his graduation and post-graduation in Journalism, his first job was as an radio personality at BIG FM, Delhi. He hosted the show Big Chai – Maan Na Maan, Main Tera Ayushmann and also won the Young Achievers Award in 2007 for it. He was the youngest recipient of the Bharat Nirman Award in New Delhi.

Khurrana made his acting debut in 2012 with Shoojit Sircar’s romantic comedy Vicky Donor, co-starring Annu Kapoor and Yami Gautam. It marked the production debut of actor John Abraham, and starred Khurrana in the titular role of a sperm donor. In preparation, he attended acting workshops and interacted with medical professionals. For the film’s soundtrack, he sang “Pani Da Rang”, which he had written and composed with Rochak Kohli back in 2003. 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”. With worldwide earnings of over ₹610 million (US$8.6 million) against a budget of ₹100 million (US$1.4 million), Vicky Donor emerged as a commercial success. At the Filmfare Awards ceremony, Khurrana was awarded trophies for Best Male Debut and Best Male Playback Singer.

In 2013, Khurrana appeared in Forbes India’s Celebrity 100 list, ranking 70th with an estimated annual income of ₹25.8 million (US$360,000). He then collaborated with Kunaal Roy Kapur in Rohan Sippy’s Nautanki Saala! (2013), a comedy based on the French film Après Vous (2005). Anupama Chopra found Khurrana to be “earnest” in it but felt that his comedic work was overshadowed by that of Roy Kapur. He also recorded two songs for the film’s soundtrack. A year later, Khurrana teamed with Yash Raj Films (as part of a three-film deal) in the romantic comedy Bewakoofiyaan (2014), co-starring Sonam Kapoor and Rishi Kapoor, about a young man who has trouble convincing his girlfriend’s father to approve of their marriage. 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”. Both Nautanki Saala and Bewakoofiyaan were commercially unsuccessful, as was his next release, Hawaizaada (2015). In it, he played the scientist Shivkar Bapuji Talpade, for which he lost weight and learnt to speak Marathi. In the same year, Khurrana collaborated with his wife, Tahira Kashyap, to write his autobiography Cracking the Code: My Journey to Bollywood.

Khurrana was born in Chandigarh. His father P Khurrana is an astrologer and an author on the subject of astrology, whereas his mother Poonam is a housewife and she is of half-Burmese descent and a qualified M.A. in Hindi. While Ayushmann remains busy with his work in Mumbai, his family still stays in Chandigarh. His brother Aparshakti Khurana is a radio jockey at Radio Mirchi 98.3 FM in Delhi and made his debut in the 2016 Aamir Khan-starrer film Dangal. The ambiance of literature at home influenced Khurrana as well and he took writing as a hobby. He also maintains a blog where he writes in Hindi and it has been received very well by his admirers. Ayushmann is known for being very close to his family and wife, Tahira Kashyap who has directed a critically acclaimed film Toffee. They are childhood sweethearts and are parents of a son and a daughter. His son, Virajveer, was born on 2 January 2012 and his daughter, Varushka, was born on 21 April 2014. In 2018, when he was promoting Badhaai Ho and Andhadhun, his wife Tahira was diagnosed with stage 0 breast cancer. Tahira’s positive outlook helped them remain rock solid through this difficult phase.

In 2018, Khurrana starred in two of the top-grossing Hindi films of the year. 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. He lobbied for the part after hearing about it from the casting director Mukesh Chhabra, and in preparation, he learnt how to play the piano and interacted with blind piano players. Udita Jhunjhunwala of Mint praised Khurrana for giving a “taut performance that balances vulnerability with craftiness” and Ankur Pathak of HuffPost found his to be “a layered, no-holds-barred performance worth applauding”. Andhadhun earned ₹4.56 billion (US$64 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. He next starred in Badhaai Ho, a comedy from director Amit Sharma about a young man whose middle-aged parents get 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”. A sleeper hit, it earned over ₹2.21 billion (US$31 million) worldwide. For Andhadhun, Khurrana won the National Film Award for Best Actor (shared with Vicky Kaushal for Uri: The Surgical Strike) and the Filmfare Critics Award for Best Actor.