Five-eighth Michael Morgan also grabbed a first-half brace as the Kangaroos, winners of 10 of the 14 versions of the tournament, ran in eight unanswered tries to set up a semi-final against New Zealand or Fiji in Brisbane next week.
Cameron Smith orchestrated Australia's attack with his usual efficiency from hooker and converted all but the last of the tries, while fullback Billy Slater made a typically lively contribution and grabbed a record-equalling 14th World Cup try.
Samoa, who got through to the last eight having not won a single one of their pool matches, were simply outclassed despite their smattering of National Rugby League players.
Australia's fourth win out of four matches in the tournament, and 10th in a row in World Cups since they lost the 2008 final to New Zealand, never looked in doubt despite the heat and humidity in the Northern Territory capital.
Winger Holmes, the first player to score five tries in a World Cup match, crossed twice in the first 17 minutes, the second a length-of-the-pitch effort that was the pick of his record haul.
"I'm speechless, I thought for sure there'd been someone who'd scored five before, I'm very honoured," he said.
"We knew it was going to be hot and wet and sweaty and our main goal was to try and turn their big forwards around. I think Smitty did a great job with that."
Co-hosts New Zealand, who were stunned by Tonga in their final pool match last weekend, face the Fijians in Wellington on Saturday.
The Tongans take on Lebanon in Saturday's other quarter-final to decide who will play the second semi-final against England or Papua New Guinea, who meet on Sunday.