Located in the Debub Wollo Zone, Ambassel woreda is bordered on the west by the Bashilo which separates it from Tenta, on the north by the Semien Wollo Zone, on the southeast by the Mille River which separates it from Tehuledere, and on the south by Kutaber; the Walano, a tributary of the Bashilo, defines most of its southern border.

Elevations in this woreda range from 1200 to 3200 meters above sea level; the divide between the drainage areas of the Nile and the Awash runs through the middle of Ambassel.

Notable landmarks include Amba Geshen, where the medieval Emperors of Ethiopia would confine their male relatives to keep them from threatening his power.

[5] The jantirar was the hereditary position of the ruler of the district of Ambassel since the reign of the first Ethiopian emperor Yekuno Amlak, but in the past ruled more domain in Bete Amhara (Wollo).

The majority of the inhabitants professed Ethiopian Orthodox Christianity, with 73.92% having reported they practiced that belief, while 25.85% of the population said they were Muslim.