South Korean teams make up half the field in the last eight of Asia's premier club competition but two second half goals ensured Al Shabab have an excellent chance of reducing the K-League contingent after the second leg in Riyadh on September 22.
Midfielder Fahad Hamad found the net for the White Lions from close range after 68 minutes and Uruguayan Juan Manuel Olivera came off the bench to add another with a cool finish in stoppage time.
The victory against the 2006 Asian champions was all the more impressive as the second goal came after Al Shabab midfielder Abdulmalek Al Khaibri had been sent off for a second yellow card.
Seongnam Ilwa's Montenegrin target man Dzenan Radoncic scored twice as the home side drew first blood in the only all-Korean tie of the round with an emphatic 4-1 victory over the Suwon Bluewings.
Radoncic put Seongnam in front after eight minutes before South Korea left winger Yeom Ki-hun equalised for the Bluewings from a free kick in the 16th.
Former Colombia international Mauricio Molina restored Seongnam's lead just after the half-hour mark with his fifth goal of the competition.
Radoncic added the third with a header midway through the second half before Suwon's Yang Sang-min turned the ball into his own net to round out the scoring eight minutes from time.
The fourth South Korean team, holders Pohang Steelers, are in Iran for the first leg of their quarter-final against Zobahan later on Wednesday before Saudi Arabia's Al Hilal host Qatar's Al Gharafa in the final last eight encounter.
