The agreement, which comes into effect on 1 April, will see Flemings Mayfair, and its sister hotel, Down Hall in Hertfordshire, benefit from Hand Picked's marketing and sales support.
Hand Picked and Flemings will also look at shared purchasing to help reduce operating costs at the businesses.
Douglas Waddell, operations director of Hand Picked Hotels, said: "For some time now we have been looking to identify a suitable London partner who will give our existing customer base a similar type of product and experience to that of the other 17 distinguished properties in the Hand Picked Hotels Group.
"In Flemings Mayfair hotel we could not have found a more suitable partner and this helps us to strengthen our distribution network with a product which is of the same standard."
Simon Scarborough, operations director of Flemings Mayfair, added: "We all are looking for creative ways to overcome these challenging market conditions. A special relationship with Hand Picked Hotels at this time will allow us to increase our sales and marketing activity and reach new customer bases without increasing our costs."
Last year Hand Picked bought three properties, comprising Hendon Hall hotel in Hendon, north London, Audleys Wood hotel in Basingstoke, Hampshire, and New Hall hotel, Sutton Coldfield, Birmingham. It has invested £3.2m in the properties since.
By Gemma Sharkey
E-mail your comments to Gemma Sharkey here.
Looking for a new job? Find your next hotel job here with Caterersearch.com jobs