Winning his fourth successive Group One race, St Mark's Basilica was giving trainer Aidan O'Brien a sixth Eclipse triumph.
Sent off the well-backed even-money favourite, the three-year-old son of Siyouni powered away from his talented opponents in the final furlong under Ryan Moore.
Tom Marquand had sent Addeybb into the lead straight from the stalls, with Mishriff for close company. St Mark's Basilica was held up in third, with El Drama last of the four as they travelled in single file.
There was no change in the order until David Egan on Mishriff drew alongside Addeybb and hit the front. It was a short-lived lead, however, as St Mark's Basilica stormed past the pair and quickly put the race to bed.
He won by three and a half lengths from Addeybb, who rallied past Mishriff to take second place.
O'Brien said: "We couldn't believe when Ryan asked him to quicken how well he did quicken. He quickens and has a great mind - he does everything.
"We felt he had stepped up since the last day and Ryan gave him a beautiful ride. I'm delighted for everybody.
"He's a relaxed traveller and doesn't use any energy. He comes on slowly and when you go for him he really turns it on. He has the mark of a special horse."
Asked about targets, the Ballydoyle trainer said: "The lads (Coolmore owners) will decide what they want to do, obviously he'd have options of maybe going to York (Juddmonte International) or Leopardstown (Irish Champion Stakes).
"I'd say something like that, depending on what the lads want to do.
"He's a horse with a lot of pace and a lot of quality."
Of Addeybb, a delighted William Haggas said: "It was a fantastic run. He fought hard as usual and he's a very consistent, genuine horse. When it's slower ground they don't quicken like that.
"The winner is obviously a very smart horse, but he fought back to beat Mishriff. It wouldn't have suited him making the running, either. He needs a good gallop.
"He might go for the King George, but he needs soft ground."
His rider Tom Marquand added: "He gave everything. He's an absolute superstar - giving that weight to the best three-year-old in Europe, and probably the world. I'm really pleased with him and he's pulled up great. No doubt William will have some nice targets for him throughout the rest of the year, and possibly into next year too, knowing him.
"I jumped and rode the race as I saw fit, and he winged the lids and showed willing. I was left alone to find a nice rhythm, and while we haven't won he's run a super race. For him on his return that was a big effort."
Winner of the Saudi Cup and Dubai Sheema Classic, as well as last year's French Derby, Mishriff could have a rematch with his Sandown conqueror at York.
John Gosden said: "He was just a bit keen early, it was his first run for a while and the ground is soft enough for him. I expect him to come on a good deal for that.
"We will head to the Juddmonte at York next, but the winner was very impressive."
David Egan was in the saddle on Mishriff and said: "On the ground over the stiff mile and a quarter on what was his first run in Britain he just got tired in that last half a furlong. He has run a good race, but he should come forward for that and progress.
"For sure I think (he has a Group One in Britain in him) as the way he travelled into the race shows how classy he is and there will be more to come."
Roger Varian, trainer of fourth-placed El Drama, said: "I thought between the two and the one (furlong) we might go and trouble the second and third, and I don't think he's quite got home over this stiff 10 (furlongs) on this ground.
"He wasn't disgraced and he'll be an interesting horse over an easy 10 or a stiff mile. I've nothing in mind, but I'll speak with the Sheikh (Mohammed Obaid Al Maktoum) about which direction we go now. He's a Listed winner, and after two shots at Group One I should think we'll look for a Group Three."