The Sudanese club won 1-0 at the Accra Sports Stadium on Wednesday. Congolese forward Vinny Kombe Bongonga scored the decisive goal in the 77th minute.
Kotoko were lucky not to suffer a humiliating defeat, as Hilal were wasteful.
The return leg is scheduled for Sudan in the first week of January.
As the two teams entered the field for the start of the game, there were huge expectations on Kotoko to find a way past their opponents.
The Kumasi-based side have not tasted the CAF Champions League group stage in 14 years so it is no surprise that Ghanaians were expectant.
But on the day, Al-Hilal dictated and secured a 1-0 victory, leaving Kotoko with a daunting task ahead of the second leg.
If football were a game of chess then it would be fair to say that the Blue Wave set unavoidable traps and completed the checkmate in impressive fashion.
The away team were organised at the back and quick on the counter. They gave the Porcupine Warriors a little taste of the plan inside just 10 minutes.
Eid Eldin left his marker for dead at the edge of the box and gave a perfect reverse pass to an open Mohammed Yusif who shockingly hit the ball wide from about seven yards.
For most of the first half, the Kotoko players tried a number of long balls without success.
After the break, the hosts pushed forward with more purpose in the first fifteen minutes.
William Opoku got closest to scoring for Kotoko, rising highest to an inch-perfect cross from Imoro Ibrahim but the opposition goalkeeper reacted well to stop the effort.
Johnson Smith, in the hope of keeping the pressure on, made some changes. Ironically, one of the substitutes made a costly mistake.
Sulley Muniru gave the ball away in a dangerous area and Vinny Bongonga finished off a swift counter to give the away side a well-deserved lead.
Kotoko huffed and puffed afterwards but they never looked close to getting the equaliser.
Their hope of getting into the group stages have taken a potentially irrecoverable hit.