Kafr Buhum is situated between the Orontes Valley to the east and south, the Masyaf Plateau to the west, the Mahardah Plateau to the north and the basaltic Harbnafsah Plateau to the southwest. The town's topography in the east and south is flatter than the north and west.
The town has a Mediterranean climate, in which winters are cold and rainy and summers warm and dry. The climate is affected by the distance from the Mediterranean Sea, 80 km (50 mi) west, and by the coastal mountains.
All sources indicate that the first part of the town's name, Kafr, derives from the Syriac word for "farm" or "village". The second part has several possible meanings, including, the plural of the Syriac word Pehmi which means "rock", the Syriac word Buhum which means "strong man", Kafr Abu which means "large house" and the Arabic Ebham, which means "thumb". The latter name derives from a local legend which holds that a thumb of Saint George is buried in Kafr Buhum's Saint George Church.
Settlement in the town probably started with the movement of people from the surrounding caves, as indicated by archaeological evidence in nearby terraces. Over time, people from different regions migrated to Kafr Buhum.
The town is ancient and was possibly established 2,000 years ago. There have been a number of important Christian spiritual figures from or associated with Kafr Buhum throughout history. Among them are Gregorios bin Fadil, the first Aleppo-based bishop of the Melkite Greek Church, who remained at the Episcopal from 1540 to 1582, performing research in theology and the Book of Proverbs.