More than 4,500 stores, as well as 14 Intu shopping centres, will dim their lights, turn down the music and share information about autism.
Shops taking part include Marks & Spencer, Clarks, Superdrug, John Lewis, Toys ‘R’ Us, Sainsbury’s and Mothercare.
Mark Lever, chief executive at the National Autistic Society, said: "The National Autistic Society is proud to be launching the first ever UK-wide Autism Hour event and is thrilled that it’s involving such a vast number of shops and businesses.
"A National Autistic Society survey found that 64% of autistic people avoid going to the shops, and 28% have been asked to leave a public place for reasons associated with their autism.
"We are confident that the National Autistic Society’s Autism Hour will provide an opportunity for autistic people and their families to use shops and services that the general public take for granted."