Sano Domain (佐野藩 Sano-han?) was a feudal domain under the Tokugawa shogunate of Edo period Japan, located in Shimotsuke Province (modern-day ), Japan. It was centered in what is now part of the city of . Sano was ruled through most of its history by a junior branch of the Hotta clan.
The Sano clan was a branch of the Oyama clan, who settled in Sano shōen during the Kamakura period, and who ruled the area over 15 generations from their impregnable mountain stronghold of Karasawayama Castle. The area was contested during the Sengoku period between the forces of the Uesugi clan and the Odawara Hōjō clan, and Karasawayama Castle withstood ten attempts to conquer it by the famed warlord Uesugi Kenshin. The 17th generation head of the Sano clan, Sano Munetsuna was defeated by Nagao Akinaga, but the Sano territories were restored by Toyotomi Hideyoshi in recognition of their efforts at the 1590 Battle of Odawara.
After Tokugawa Ieyasu took control over the Kantō region in 1592, he confirmed Sano Nobuyoshi as daimyō of a 35,000 koku holding. This was the start of Sano Domain. However, the Sano clan was dispossessed of their holdings in 1614 for reasons which are still unclear.