Abraham was born in Mumbai to a Malayali father and a Parsi mother. His father is an architect from Alwaye, Kerala; his mother is named Phiroza Irani. Abraham's Parsi name is "Farhan" while his father being a Syrian Christian, named him "John". He has a younger brother, Alan.

He studied at the Bombay Scottish School, Mahim in Mumbai and did his MMS[clarification needed] from the Mumbai Educational Trust (MET).

Abraham started his career appearing in the music video of a song, "Surma", by a Punjabi singer, Jazzy B. He then joined the 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 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 in which he co-starred with Bipasha Basu. The film was a moderate box-office success and his performance was recognised by critics. It was while making of this film that Abraham and Basu started dating each other.

His next film, a paranormal thriller Saaya (2003), was a commercial and critical failure. It was followed by a number of failures, including Pooja Bhatt's directorial debut Paap (2004) and Ahmed Khan's Lakeer – Forbidden Lines (2004).

He appeared, in a villainous role, as Kabir 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 major role in the critically acclaimed film 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.