Stephen Wiltshire was born in London in 1974 to Caribbean parents. He grew up in Little Venice, Maida Vale, London.

At the age of five, Wiltshire was sent to Queensmill School in London where he expressed interest in drawing. His early illustrations depicted animals and cars; he is still extremely interested in American cars and is said to have an encyclopaedic knowledge of them. When he was about seven, Wiltshire became fascinated with sketching landmark London buildings. After being shown a book of photos depicting the devastation wrought by earthquakes, he began to create detailed architectural drawings of imaginary cityscapes.

Wiltshire can look at a subject once and then draw an accurate and detailed picture of it. He frequently draws entire cities from memory, based on single, brief helicopter rides. For example, he produced a detailed drawing of four square miles of London after a helicopter ride above that city. His nineteen-foot-long drawing of 305 square miles of New York City is based on a twenty-minute helicopter ride. He also draws fictional scenes, for example, St. Paul's Cathedral surrounded by flames.

In 2006, Wiltshire was made a Member of the Order of the British Empire (MBE) for services to art. In the same year, he opened a permanent gallery on the Royal Opera Arcade in London. In 2011, Wiltshire was made an honorary Fellow of the Society of Architectural Illustration (SAI). In January 2015, Wiltshire was also made an honorary Fellow of The Scottish Society of Architect Artists.

According to wikipedia