The talented pair not only have to fight for family honour, but also have to face the brilliant three-year-old filly Enable, winner of the English and Irish Oaks.
"Both horses are well, but the ground is the thing. Idaho has form with ease in the ground, and Highland Reel has a little bit, too. We would be happy with good to soft and hopefully it won't get any worse than that," said O'Brien.
The Ballydoyle trainer's first success in the mile-and-a-half feature came with Galileo in 2001 and now his son, Highland Reel, bids to become only the third horse to win the prestigious prize two years running after Dahlia (1973-74) and Swain (1997-98).
Victory for Highland Reel would take the five-year-old's prize money haul to £6.5milliion and his Group One wins to seven.
"Highland Reel is an incredible horse. He's tactically very quick, he's very like his dad. He stays well, but is also very quick out of the gates, very good to get a position and he would absolutely die for you. It's incredible, he's so genuine," said O'Brien.
"He handles fast ground, mile and a quarter to a mile and a half. On the big day in the big races, you see he gets his blood up when he needs to."
Ulysses, trained by Sir Michael Stoute, is seeking to win both the Coral-Eclipse and the King George in the same season. It was last achieved by Opera House in 1993, one of five winners of this race for Stoute.
"We are very happy with him. As far as the trip is concerned he has won a Gordon Stakes and run a very solid race at Santa Anita in the Breeders' Cup Turf," said the Newmarket handler.
"He is more settled this year and relaxes better. That is to his advantage. We go there hopeful and hoping there is not too much rain. His preparation has gone well. I hope the ground will not be too testing."
In the Coral-Eclipse, Desert Encounter belied his odds of 50-1 to finish third behind Ulysses, and his trainer David Simcock believes there is more to come from the five-year-old.
"He ran very respectably in the Eclipse and the plan was always to go to the King George afterwards," he said.
"He's an improving horse who handles any ground and stays a mile and a half well."
Enable's trainer John Gosden also saddles Jack Hobbs, who showed what a good horse he is with ease in the ground when lifting the Dubai Sheema Classic in March.
Gosden said: "He was very fortunate he got that ground in Dubai. He was not that fortunate at Royal Ascot. He is back to probably his best distance and with give in the ground, it should play to his strengths."
Jack Hobbs carries the Godolphin colours, as does Benbatl who, along with Enable, represents the Classic generation.
Benbatl landed a deserved success in the Hampton Court Stakes at Royal Ascot after good efforts in the Dante and the Derby.
"Benbatl won well at Royal Ascot and is improving with time," trainer Saeed bin Suroor told www.godolphin.com.
"His latest piece of work on Monday went nicely and good to soft ground will be fine for him."
Clive Cox has been happy to see rain for My Dream Boat, who is a tip-top performer on soft ground as he showed when beating Found in the Prince of Wales's Stakes at Royal Ascot in 2016.
"He's not as effective when it's too firm and the recent rainfall has been very welcome. It looks like he will get his favoured conditions," said the Lambourn trainer.
"He ran a pleasing race in France last time and while he is quite laid-back at home, he's been giving us the impression he's at the top of his game."