Zamalek, five times former champions of Africa, were beaten by a side playing in an African club competition for the first time.
Welayta Dicha have now qualified for the Confederation Cup play-offs where they will face one of the African Champions League last-32 losers.
The Ethiopians came armed to Egypt with a 2-1 advantage from the first leg of the continent’s second-tier club tournament.
On Sunday, the scoreline was reversed with Zamalek winning their home leg 2-1.
Ahmed Madbouli had given the Egyptians a 2-0 lead, but Welayta Dicha levelled the aggregate score to 3-3 with a goal from Abdel-Samad.
That took the contest into a tense penalty shoot-out in front of Zamalek’s own fans.
The pressure told on the hosts who missed two of the spot-kicks, with the visitors winning 4-3 to record a famous victory.
It is a further blow for Zamalek, whose arch-rivals Al Ahly won the domestic league title in Egypt last week.
Zamalek are currently third in the Egyptian league standings.
Source: BBC Sport