The clash at Amahoro Stadium saw the Sudanese champions end a long wait for a win over their rivals by capitalising on key mistakes.
Al-Hilal took the lead deep into first-half stoppage time when Mohammed Abdel Rahman calmly converted a penalty after a costly error by goalkeeper Denis Onyango.
The momentum carried into the second half as Jean Claude Girumugisha doubled the advantage four minutes after the restart with a low finish from the edge of the area.
Sundowns raised the tempo and pulled one back through substitute Arthur Sales just after the hour mark, but despite sustained pressure, they could not find an equaliser.
Al-Hilal held firm to secure a vital win, moving top of the group on eight points, while Sundowns remain second with five.