Williams sisters Serena and Venus had been hoping to provide fans with the first all-Williams sisters clash at a Grand Slam since the 2009 Wimbledon final in the semi-finals.
The World No 1 did her part with a clubbing 6-2, 6-2 demolition of Dominika Cibulkova but Venus was unable to exploit the thigh injury that badly affected the 19-year-old Madison Keys's mobility.
Keys overcame a leg injury to secure a 6-3, 4-6, 6-4 victory over Venus.
Serena, battling the effects of a cold that has made her hoarse, was not going to allow last year's beaten finalist to dictate the flow of the game as the Slovak had done against twice champion Victoria Azarenka in the fourth round.
"I've been sick the past few days. It's just getting worse and worse. But hopefully it will start getting better," she said.
"I heard it's a virus going around with a lot of the players. I think I caught it."
The American, who had comfortably won the pair's previous four encounters, hammered down 15 aces, to Cibulkova's one, and belted 31 winners to 13 by the 11th seed to advance to her sixth semi-final at Melbourne Park.
Ominously every other time she made the semi-finals, she went on to win the title.
"When she has this day, it's tough to play against her," Cibulkova said.
"I just felt under so much pressure. It was a good day for her."
Keys was a toddler when Venus made her first Grand Slam final in 1997 and had been inspired to take up the sport by watching the seven-time Grand Slam champion.
While the pair had met at Charleston in 2013, Keys was plainly nervous about playing the 34-year-old at a Grand Slam.
The clean ball striking and power hitting that had destroyed players of the calibre of double Wimbledon champion Petra Kvitova was replaced with mishits and overcooked groundstrokes.
The 19-year-old, now coached by former number one Lindsay Davenport, however, showed her maturity and mental toughness once she settled to overpower Venus and battle through the injury that temporarily derailed her in the second set.
"It was definitely a flashback to Wimbledon for me," Keys said of the injury that forced her to take an injury break while trailing 4-1 in the second set.
"It was quite an overwhelming moment and scary ... and I had the nightmare of 'I don't want this to happen again', luckily the pain meds kicked in and I was able to get through it."