Gautam was twenty when she moved to Mumbai to pursue a career in movies.[14] She made her television debut with Chand Ke Paar Chalo, which was followed by Raajkumar Aaryyan. Following this, she played her most notable role in Yeh Pyar Na Hoga Kam,[15] which aired on Colors.[16] Furthermore, she participated in the reality shows Meethi Choori No 1 and Kitchen Champion Season 1.
Yami Gautam ventured into the world of glamor with the television show Chand Ke Paar Chalo, which was followed by the hit TV serial Yeh Pyaar Na Hoga Kum, aired on Colors.
Yami made her film debut in the Kannada film Ullasa Utsaha in 2010. The movie bombed at the box office, but her performance received favorable reviews. Then in 2011, she appeared in her first Telugu film Nuvvila. Directed by Ravi Babu, this rom-com was a hit and received great reviews from the audiences and critics alike.
Her Bollywood breakthrough came with Shoojit Sircar`s Vicky Donor, opposite Ayushmann Khurrana in 2012. Produced by actor John Abraham, the movie was a commercial and critical success, and Yami was praised for portraying a young and opinionated Bengali girl. About her performance, famous critic Taran Adarsh noted, "Popular television actress Yami Gautam makes an imposing debut. She adds enormous value to the movie by her act, screen presence, and striking looks. She`s truly admirable towards the latter part of the film." For this film, Yami also won her first IIFA Award.
In 2014, she appeared in a leading role in Total Siyapaa, and Action Jackson, but both the films failed to generate any profit. Her next film was the crime thriller Badlapur, in which she starred alongside Varun Dhawan, Huma Qureshi, Nawazuddin Siddiqui, Vinay Pathak, Divya Dutta, and Radhika Apte. The film was nominated for Best Film at the 61st Britannia Filmfare Award.
In February 2016, she starred in Divya Khosla Kumar`s romantic-drama film Sanam Re with Pulkit Samrat and Urvashi Rautela. The film received a lukewarm response at the box office, but Yami Gautam and Pulkit Samrat`s chemistry was well applauded. Her other 2016 release includes Junooniyat, also opposite Pulkit Samrat. In 2017, she starred along with Hrithik Roshan in Kaabil, which was commercially hit. Her 2019 release include Uri: The Surgical Strike and Bala.