However, after a steady pace was set in the two-and-a-half-mile showpiece, Murtagh pressed go turning from home and led a long way out.
That burst of pace broke the rest of the field and, despite young pretender Patkai coming out of the pack to chase him home, the eight-year-old kept on producing and strode away to a momentous victory.
O'Brien said: "Unbelievable - that's all I can say. I was so sick this morning as I really believed this couldn't happen.
"History is very hard to change, we knew we had a wonderful horse but usually fairytales don't come true.
"History is very hard to change, we knew we had a wonderful horse but usually fairytales don't come true.
"You dream and dream and dream, we were in this position and we never would be again - great things can happen.
"It's unbelievable and I want to say a big thanks to everyone involved."
Murtagh was actually one of the first of the principals at work before the turn for home, but his mount was more than willing to respond and the advantage he took early in the straight proved decisive.
Patkai could only get within three and a half lengths of the brilliant champion, while Geordieland, runner-up for the last two years, had to make do with third this time around, 15 lengths further adrift under Shane Kelly.
"Muhammad Ali told everyone he was the greatest and he was, and Yeats has shown everyone today that he is the ultimate heavyweight champion," said Murtagh.
"Muhammad Ali told everyone he was the greatest and he was, and Yeats has shown everyone today that he is the ultimate heavyweight champion," said Murtagh.
"I had no doubts. After Navan I looked at Aidan and he told me 'he'll be grand for Ascot'.
"We kept saying the ground was too soft at Navan but nobody believed us and people tried to pick holes in him. He loves fast ground, he loves Royal Ascot and he comes alive here.
"This is one the greatest days of my riding career and the feeling I had coming past the line for the horse alone was incredible.
"I've had a good week but for the horse to win four Ascot Gold Cups is fantastic and the crowd turned out in force to see him. It's good for racing, and Yeats is everything that's positive about racing."