Sergej Milinkovic-Savic powered through the penalty area to meet Malcom's cross in the 15th minute with a firm header that gave Al Hilal the lead.
Two goals in two minutes at the end of the half put the Saudi side in control, Joao Cancelo latching onto Malcom's through pass to thump his shot home in the 42nd minute to double the lead.
Cancelo turned provider in the 44th minute, the Portuguese fullback setting up Marcos Leonardo to score from the edge of the six-yard box.
Al Hilal could have won by a larger margin, but Aleksandar Mitrovic saw his 71st minute penalty saved by Paulo Victor while Malcom also hit the post for the Saudi Pro League champions.
Earlier in the evening, Al Wasl of the United Arab Emirates picked up a 1-0 win over Uzbekistan's Pakhtakor in Tashkent, with Moroccan defender Soufiane Bouftini heading in the game's only goal in the 64th minute.
The wins for Al Hilal and Al Wasl see them join Iran's Esteghlal and Al-Ahli of Saudi Arabia as the only teams to pick up three points from their opening game in the league phase in west Asia.
Twelve clubs from the eastern and western halves of the continent will play eight games using the Swiss League format in the opening phase of the competition, with the top eight sides on each side of the draw advancing to the knockout rounds.
The last 16 will be played in March with the quarter-finals, semi-finals and final, which will be held on the 4th May, all due to be played on a centralised basis in Saudi Arabia.