Works by Matisse, Picasso, Gustav Klimt and Ben Nicholson will be offered at auction at Christie's in February, as well as Sting's Steinway piano.
The auction house said the couple had collected the works "with passion and knowledge" over 20 years.
One painting, Nicholson's March 55 (amethyst) could fetch up to £500,000.
The British abstract painter's 1955 work previously hung in the music room at their house in Queen Anne's Gate. It will be auctioned alongside Robert Mapplethorpe photographs, Matisse's Jazz series and Picasso's lithograph Le Corsage a Carreaux.
Prints by Georges Braque and Rene Magritte, as well as well as more contemporary artists such as Carsten Holler, will be auctioned alongside 20th century furniture and lighting by Post-War masters including Yves Klein.
Andy Waters, head of private collection sales for Christie's London said the Queen Anne's Gate home had "effortlessly combined luxury, rarity and colour".
"Each work of art was carefully chosen and the resulting collection is a testament to Sting and Trudie Styler's informed eye for art and design," said Waters.
The couple, whose four children are now grown up, decided to sell the works after buying a new home in London's Battersea power station development. A Christie's spokesperson said they felt it was "time for a change".
More than 200 separate lots are due to be auctioned on 24 February 2016, with estimates ranging from £1,000 to £500,000.
Christie's said the collection also demonstrated the couple's support for young contemporary artists. It includes works by Emily Allchurch and Giles Alexander and a "striking" series of panels by Russian artist Veronica Smirnoff, specially commissioned for the staircase of the house.
Musician Sting and wife Trudie Styler are selling more than 200 items from their art collection, previously housed in their former family home in London.