The campaign will aim to increase awareness of the family-owned car rental company, and dramatise its brand promise – "Drive first class, pay economy".
The agency won the above-the-line UK account after a two-way pitch that began in February and was run by the client.
There was no incumbent on the account.
Jung von Matt, Sixt’s global lead agency, and OMD, its media agency, are unaffected by the appointment.
Per Vögerl, the managing director of commercial of Sixt UK, said: "Sixt has been successfully operating in the UK for almost 20 years, yet we’ve never undertaken a true introductory brand campaign to launch our position in the market.
"Grey is the perfect partner with which to do so. We particularly bought into their culture, the strength of their integrated creative work and their innovative use of channels."
Grey’s first work will break in June. The campaign will comprise press, digital, airport billboards and a tube station "takeover".
Lucy Jameson, the chief executive of Grey London, said: "Sixt is a brand with huge potential. It has been operating in Germany for more than 100 years to great success and has become known for its innovative, direct and bold advertising in the process.
"That’s exactly the kind of business we want to be working with and exactly the kind of work we want to be making."