She has a BA in Creative Writing from Hamilton College, and an MFA from the MFA Program for Poets & Writers at the University of Massachusetts Amherst, where she was influenced by the Kashmiri poet Agha Shahid Ali. Shamsie wrote her first novel, In The City by the Sea, while still at UMass, and it was published in 1998. It was shortlisted for the John Llewellyn Rhys Prize in the UK, and Shamsie received the Prime Minister's Award for Literature in Pakistan in 1999. Her second novel, Salt and Saffron, followed in 2000, after which she was selected as one of Orange's 21 Writers of the 21st century. Her third novel, Kartography, received widespread critical acclaim and was shortlisted for the John Llewellyn Rhys award in the UK. Both Kartography and her next novel, Broken Verses, have won the Patras Bokhari Award from the Academy of Letters in Pakistan. Her fifth novel Burnt Shadows was shortlisted for the Orange Prize for Fiction. Her books have been translated in a number of languages.
She is the daughter of the famous literary journalist, compiler and editor Muneeza Shamsie, niece of Attia Hosain and granddaughter of the writer Begum Jahanara Habibullah. Her sister Saman Shamsie used to be a college counselor and taught O-level Physics and SAT writing and reading at Karachi Grammar School.
In 2009, Kamila Shamsie donated the short story "The Desert Torso" to Oxfam's Ox-Tales project – four collections of UK stories written by 38 authors. Her story was published in the Air collection.