Zareen Khan was born on 14 May 1987 in Mumbai, Maharashtra, India, into a Muslim Pashtun (also known as Pathan or Afghan) family. She speaks Hindi, Urdu, English and Marathi, and some Pashto. She completed her intermediate at Rizvi College of Science, Mumbai.

Zareen Khan made her screen debut with a leading role in the 2010 Anil Sharma's period film Veer co-starring with Salman Khan for which she was nominated for the Zee Cine Award for Best Female Debut. Khan garnered recognition from her item number "Character Dheela" in Ready, which was one of the highest-grossing Bollywood films of 2011. Khan earned commercial success in Bollywood with Sajid Khan's Housefull 2. The following year, Khan made her Tamil debut in the Tamil film Naan Rajavaga Pogiren, in which she did an item number in the song "Malgove". She achieved further success for her leading role in the 2014 romantic thriller Jatt James Bond, a box-office success and followed it with a leading role in the highly successful Vishal Pandya's film Hate Story 3.

In 2011, Khan did the item number "Character Dheela" with Salman Khan in Anees Bazmee's Ready, parodying characters from Mughal-e-Azam, Sholay and Shri 420 and it was the highest-grossing Bollywood film of 2011.

Khan's second release was Sajid Khan's comedy film Housefull 2, a sequel of Housefull and Hindi remake of the Malayalam film Mattupetti Machan. The film revolves around two cousins Henna and Bobby, the two daughters of the Kapoor family who hate each other very much, a model Jlo love interest of Jolly, the son of Jagga Daku and four Best friends Sunny, Max, Jolly and Jai who fall in love with her. Khan played the role of JLo, a model who is in love with Jolly, played by Ritesh Deshmukh and featured her alongside an ensemble cast including Akshay Kumar, Asin, John Abraham and Jacqueline Fernandez. Khan earned critical acclaim for her performance, with Taran Adarsh stating, "Zarine act more as eye candy. She appears typical sultry and enticing selves; and is befit in her own space." Housefull 2 was among the highest-grossing Bollywood films of 2012.

In 2013, Khan made her Tamil debut in Vetrimaaran's Naan Rajavaga Pogiren, in which she did an item number in the song "Malgove" alongside Nakul Jaidev. She was appreciated for the song. Taran Adarsh commented, "Zarine Khan's song is high on Energy."

Khan's first release of 2014 was Rohit Jugraj's Punjabi film Jatt James Bond, her first role outside Bollywood. She featured in the role of a Lalli, an innocent Punjabi woman alongside Gippy Grewal. The film received positive reviews from critics, and her performance was particularly praised. Film critic Komal Nahta wrote "Zarine Khan delivers an award-winning performance. She is extraordinary and lives the role of Lalli, making every scene in which she appears immensely watchable for her brilliance!"

In 2015, Khan appeared in erotic thriller film Hate Story 3, in which she played Siya. The film was a commercial success and got Khan further recognition. She then appeared in a music video "Pyaar Manga Hai" with Ali Fazal. The song was sung by Armaan Malik and Neeti Mohan. In 2016, Khan did an item number in the film Veerappan. The same year, she also appeared in another item song named "Mahi Ve" in the film Wajah Tum Ho.

In 2017, Khan appeared in Aksar 2. In the film, she was seen romancing with Gautam Rode, and the first poster of the movie was released on 4 August 2017 on YouTube. Umesh Punwani from Koimoi.com wrote ''Zareen Khan does good in parts but sadly she is majorly used for the skin show. Years into Bollywood she still can’t emote her expressions properly.'' Bollywood Hungama disliked Khan's performance and wrote ''Zareen Khan is strictly okay and though she is sizzling, it’s done just for the heck of it. She tries to be the female Emraan Hashmi but it doesn’t work for her. Performance-wise, she doesn’t give her best shot.''

As of January 2018, Khan is committed to star in upcoming action film One Day, in which she will portray the role of a police officer and the film will be directed by Ashok Nanda.