Kaif began her modeling career at age fourteen; her first assignment was for a jewelry campaign. She continued modeling in London. Her modeling work led to her discovery by London-based filmmaker Kaizad Gustad, who gave her a part in his film Boom (2003). The film, which starred Amitabh Bachchan and Gulshan Grover, failed to make an impact.
In 2005, Kaif made a cameo in Ram Gopal Verma's drama Sarkar, as Abhishek Bachchan's girlfriend. The same year, she landed her first major role in David Dhawan's adaptation of Cactus Flower, Maine Pyaar Kyun Kiya, where she was paired opposite Salman Khan. The film became a moderate success.
The following year, she was paired opposite Akshay Kumar for the first time in Raj Kanwar's box-office flop Humko Deewana Kar Gaye. In 2007, Kaif appeared in Vipul Shah's romantic-comedy Namastey London, alongside Rishi Kapoor, Akshay Kumar and Clive Standen. Upon its release, the film became a major hit.
Her next release was David Dhawan's unofficial remake of Hitch, Partner, where she starred alongside Salman Khan, Govinda and Lara Dutta. This too was box-office success. Her final film of 2007, Welcome, directed by Anees Bazmee and co-starring Akshay Kumar, Paresh Rawal and Anil Kapoor, was declared a blockbuster.
Her first release of 2008 was Abbas-Mustan's hit action-thriller Race; she played Saif Ali Khan's secretary, Sophia. The film also featured Anil Kapoor, Bipasha Basu and Sameera Reddy in leading roles.
Kaif was next seen in Anees Bazmee's action comedy Singh Is Kinng, portraying Akshay Kumar's love interest and Ranvir Shorey's fiancée. After its release, the film was declared a blockbuster and emerged as the third highest grossing film of 2008. Kaif's final release of he year, Subhash Ghai's Yuvvraaj, was a commercial failure, but its script made its way into the Library of the Academy of Motion Picture Arts & Sciences for artistic merit, original screenplay with a substance.
Kaif's first release for 2009 was Kabir Khan's terrorism drama New York, with John Abraham and Neil Nitin Mukesh. It was a critical and commercial success. Kaif received her first nomination in the Filmfare Award for Best Actress category.
In November 2009, she appeared along with Ranbir Kapoor, in Rajkumar Santoshi's blockbuster comedy Ajab Prem Ki Ghazab Kahani, as Jennifer Pinto.
Kaif's first film of 2010 was Prakash Jha's political thriller Raajneeti, where she appeared opposite Ranbir Kapoor and Arjun Rampal, the film performed extremely well at the box office.
Her last release was Farah Khan's brainless comedy Tees Maar Khan with Akshay Kumar. The film received mainly negative reviews and was declared a flop. However, Kaif's item number Sheila Ki Jawani became a major chartbuster.
