In this podcast episode of Kadaipoma with Parveen sultana ft. Vijaysethupathy, Vijay Sethupathi was born and raised in Rajapalayam until he moved to Chennai in class six. He lived in Ennore located in North Chennai. He attended the MGR Higher Secondary School in Kodambakkam and Little Angels Mat. Hr. Sec. School. According to Sethupathi, he was a "below-average student right from school" and was neither interested in sports nor extra-curricular activities. At age 16, he auditioned for a role in Nammavar (1994) but was rejected due to his short height.

Sethupathi did a series of odd jobs for pocket money: salesman at a retail store, a cashier at a fast-food joint, and a phone booth operator. He graduated with a Bachelor of Commerce degree from the Dhanraj Baid Jain College (an affiliate of the University of Madras) in Thoraipakam. A week after he finished college, he joined as an account assistant at a wholesale cement business. He had to take care of three siblings and moved to Dubai, United Arab Emirates as an accountant because it paid him four times more than what he was making in India. While in Dubai, he met his future wife, Jessie, online. The two dated, eventually marrying in 2003.

Unhappy with his job, he returned to India in 2003. After a brief stint in the interior decoration business with friends, he joined a marketing company that dealt with readymade kitchens when he saw Koothupattarai’s poster. He recalled director Balu Mahendra remarking that he had a "very photogenic face", and motivated him to pursue an acting career.