John Abraham started his modelling career appearing in the music video of the song "Surma" by Punjabi singer Jazzy B. He then joined a media firm Time & Space Media Entertainment Promotions Ltd., which, however, closed because of financial problems. Later, he worked for Enterprises-Nexus as a media planner. In 1999, he won the Gladrags Manhunt Contest and went to the Philippines for Manhunt International, where he won second place. Following this, he was signed by Carrie Models in Singapore and did some modelling there; he later modelled in Hong Kong, London and New York City. He also appeared in a number of commercial advertisements and in other music videos for singers including Pankaj Udhas, Hans Raj Hans and Babul Supriyo. To improve his acting skills, Abraham joined the Kishore Namit Kapoor acting laboratory and completed an acting course while juggling modelling assignments.
Abraham made his acting debut with Jism (2003), a thriller film which according to Box Office India, was "above average" grossing 132,500,000 Rs.
His next films included a paranormal thriller Saaya (2003), Pooja Bhatt's directorial debut Paap (2004) and Ahmed Khan's Lakeer – Forbidden Lines (2004).
He played the role of Kabir – the main antagonist in Dhoom in 2004, an action film produced by Yash Raj Films. The film was one of the highest grossing films of that year.
In 2005 he starred in the supernatural thriller Kaal and the comedy Garam Masala both of which did well at the box office. Later that year, he had a role in Water, which portrayed the tragic fate of Hindu widows in British India of the 1930s. The film was written and directed by independent Canadian film-maker Deepa Mehta. It was popular internationally, and was nominated for the 2006 Academy Award for Best Foreign Language Film at the 79th Academy Awards.
In the summer of 2006, Abraham performed at the "Rockstars Concert" along with fellow Bollywood actors Salman Khan, Zayed Khan, Kareena Kapoor, Esha Deol, Shahid Kapoor and Mallika Sherawat. In that same year, he starred in the films Zinda, Taxi No. 9211, Baabul and Kabul Express. Among these Taxi No. 9211 and Kabul Express were substantially successful.
Nikhil Advani's multi-starrer Salaam-e-Ishq: A Tribute to Love was Abraham's first release in 2007. The movie failed to do well at the Indian box office, though it did well in the overseas markets. His last two 2007 releases included the arthouse thriller No Smoking and the sports film Dhan Dhana Dhan Goal.
In 2008, Abraham starred alongside Abhishek Bachchan and Priyanka Chopra in Dostana, his only release that year. His first release of 2009 was a production by Yash Raj Films, New York.
He has a fashion line— branded JA Clothes — which primarily features his favorite article of clothing, jeans.
In 2011, was seen in the films Aashayein and Jhootha Hi Sahi. Both of the films turned out to be box office failures. Lately, Abraham has appeared in films Force (2011), Desi Boyz (2011), and Housefull 2 (2012). His first film of 2013 was Race 2 which was a multi starrer and a comercial hit while his second release was I, Me Aur Main, which did average business. He is currently working on Shootout at Wadala, in which he will be portraying the role of Manya Surve.
His debut film as a producer was titled Vicky Donor (2012) and featured Ayushmann Khurrana, Annu Kapoor and Yami Gautam. Abraham also appeared in an item-number for the film. It opened to positive response, and turned out to be a critical and commercial success. He is currently working on his second production, Madras Cafe which will also be directed by Shoojit Sircar. Abraham has also announced his ideas on Hamara Bajaj, an upcoming reality film he is planning with most of the cast & crew of Vicky Donor.