Edinho opened the scoring for the hosts after five minutes of the Group D encounter when the Brazilian rifled a shot into the bottom corner but Al Hilal levelled just after the break as Mohammad Al Mahyani fired home from close range.
However, substitute Paulo Zaltron put Mes back in front with 12 minutes remaining when he smashed the ball into the roof of the net from a tight angle after bursting into the box.
Al Hilal's Mohammed Al Fraidi was then sent off in the dying minutes before Mes made the points safe in injury time when Mahdi Rajabzadeh scored with a cute backheel after Al Hilal keeper Abdulaziz Al Daeyea had lost possession after wandering out of his area.
And a last-minute equaliser for Al Ahli saw them hold Al Sadd 2-2 in Doha and confirm the Iranians' progress after inflicting Al Hilal's first defeat of the competition.
Mes came into the game knowing three points was a must and got off to a great start when Edinho latched on to keeper Abbas Mohammadi's clearance and surged into the left hand side of the box before drilling a low strike into the corner across keeper Al Daeyea.
Al Hilal almost hit back immediately when Al Fraidi jinked past a couple of Mes defenders but side-footed wide of the far post from six yards.
Al Mahyani then saw a header from Omar Al Ghamdi's cross hit the post in the 11th minute and Mes threatened at the other end when Milad Sheikhfakhroddini drove into the box and rode Saeed Al Dawsari's sliding challenge but Al Daeyea did excellently to tip his fierce drive over the bar.
To the Mes fans' dismay, Al Hilal levelled six minutes after the restart. Al Fraidi managed to dance past a couple of half-hearted challenges in the box before poking the ball back to Al Mahyani to rifle home from close range.
Mohammadi did well low to his right to keep out Al Mahyani's 25-yard drive and Edinho headed wide from a tight angle before Zaltron's introduction turned the game.
The 29-year-old Brazilian breezed in between two defenders down the right side of box and left Al Daeyea with no chance as he buried the ball into the roof of the net.
Al Fraidi was dismissed with one minute left following as tempers boiled over before Rajabzadeh sealed victory in stoppage time.
Al Daeyea rushed out to beat the midfielder to a through ball but with his limited dribbling skills he proceeded to give the ball straight to Gholam Abbas Ashoubi, who dribbled into the box and squared to Rajabzadeh, who back-heeled the ball past a defender into the empty net.