Uber will not be issued with an operating licence after its current deal expires on September 30, Transport for London (TfL) has announced.
TfL concluded that the minicab app is "not fit and proper" to operate in the English capital due to concerns which have "public safety and security implications".
These include its approach to reporting serious criminal offences and how it carries out background checks on its drivers.
Uber was given just a four-month temporary licence in May.
Mayor of London Sadiq Khan said in a statement: "I want London to be at the forefront of innovation and new technology and to be a natural home for exciting new companies that help Londoners by providing a better and more affordable service.
"However, all companies in London must play by the rules and adhere to the high standards we expect - particularly when it comes to the safety of customers. Providing an innovative service must not be at the expense of customer safety and security.
"I fully support TfL's decision - it would be wrong if TfL continued to license Uber if there is any way that this could pose a threat to Londoners' safety and security.
"Any operator of private hire services in London needs to play by the rules."Labour MP Wes Streeting, chairman of the All Party Parliamentary Group on Taxis, said: "This is a courageous decision by the Mayor and Transport for London, finally drawing a line in the sand to make it clear that no company, however big and powerful, will be allowed to flout our laws and regulations or jeopardise Londoners' safety without facing serious consequences.
"Uber has not shown itself to be a fit and proper operator. It stands accused by the police of failing to properly handle serious allegations of rape and sexual assault of passengers.
"It had to be dragged through the courts to recognise its responsibility to provide even the most basic rights and protections to Uber drivers. Its business model is based on saturating London's taxi and private hire market to drive its competition off the road.
"That's why major cities across North America and Europe have already banned Uber from operating on their roads."