Kassala's location along the main Khartoum-Port Sudan highway makes it an important trade center.

[3] In the 18th and 19th centuries, the city was a key node in the west–east trade route, linking the coastal ports of Massawa and Suakin with the Sudan and farther west.

[4] The city was conquered by Ottoman soldiers of Egyptian viceroy Muhammad Ali in 1840 during his military offensive into Sudan.

The Italians then occupied the city with brigade-sized units:[5] on July 4, 1940 the Italians started their offensive with 2,500 men (and one brigade of cavalry) supported by 24 tanks, while to defend Kassala for Britain there were 1,300 colonial soldiers with their British officers who -after some initial heavy fighting- were easily defeated.

The Italians later appointed as mayor of Kassala the future hero of Eritrean independence, Hamid Idris Awate.

[9] The Khatmiyya Mosque, built in 1840 by the Ottomans and damaged during the Mahdist War, is the city's most important cultural site.