The Danish sixth seed missed out on converting any of the six break points he earned in the opening set, and then found himself a set and 4-2 down after surrendering his own serve with two successive double faults.
Through all that mental turmoil, he never lost belief and he came storming back with some phenomenal shot making as he became the first Dane in 65 years to reach the Wimbledon quarter-finals.
It was little wonder he was left screaming into the skies and thumping his chest after the near three-and-a-half hour battle ended when Dimitrov's backhand floated into the tramlines on Rune's first match point.
"It was a crazy match," summed up a hugely relieved Rune. "Grigor pushed me to the limit."
Once tipped as a future Grand Slam champion, Dimitrov has not even made it into the final of any of the four majors. As he clocked up his 51st Grand Slam appearance at Wimbledon, he knew that only three semi-final showings made for a poor return.
But if he harboured hopes that this might be the week when he will finally go all the way, Rune handed him a brutal reality check.
For a set and half Dimitrov looked like he would back up his win over American 10th seed Frances Tiafoe by knocking out another Top 10 contender.
Such was his determination to win the points that mattered, he kept slipping and sliding over as he chased down every ball and still managed get back on his feet to punch away the winners.
But sustaining that level of intensity for over three hours was a nigh on impossible task and once Rune unexpectedly broke back in the second set to level it a 4-4, it always seemed that the Dane's younger and fresher legs would carry him over the finishing line.
Rune puffed out his cheeks in relief when he won an electrifying 19-shot rally to seal the second set.
The two went toe-to-toe in an absorbing third set, with neither earning a break point. But a moment of misjudgement at 5-3 down in the tiebreak proved to be Dimitrov's undoing.
Convinced that Rune's shot had landed beyond the baseline, the Bulgarian stopped the point to challenge Hawkeye. But it seemed that Dimitrov's eyesight had let him down badly as Hawkeye called the ball in, handing three set points to his opponent.
Rune converted the second, ironically also stopping the ball in its tracks to challenge Hawkeye - and his eyesight proved to be much sharper.
That appeared to leave Dimitrov deflated and when he surrendered his serve in the sixth game of the fourth set by producing successive double faults, it was effectively game over.
He will next meet fellow 20-year-old and world number one Carlos Alcaraz who beat big-hitting Italian Matteo Berrettini (27) for a place in the semi-finals.
