The agency will now produce all of the creative and strategic thinking for the haircare brand, which is understood to be seeking a more creative approach to its ads.
The account was previously handled by JWT, which will continue to work on global activation through its network.
In 2007, JWT London produced an ad for the brand that saw the pop group Girls Aloud kidnapping a dowdy woman and transforming her into a pop star beauty with the aid of Sunsilk shampoo.
Santo, the WPP-backed Argentinean agency, launched in London in May this year. It is run by Pablo Minces, the creative director, and Martin Cole, a former WPP consultant.
A spokesman for JWT said the appointment of Santo was for one strategic project.