Generations will collide as Serena Williams clashes with rising teenage star Madison Keys in a high-stakes, all-American semi-final showdown at the Australian Open on Thursday.

Williams is not only defending her world No 1 ranking, but playing for her first finals berth in Melbourne since 2010 as she continues her pursuit for a watershed 19th grand slam crown.

"Gosh, it's been so long," the five-time champion said after swatting aside last year's surprise runner-up Dominika Cibulkova 6-2 6-2 on Wednesday.

"It's finally good to get past the quarter-finals or the fourth round. I forgot what it's like for this place."

Standing in the way of the 33-year-old and Saturday's title match is the brightest young prospect in American tennis after Keys ended the vintage run of Serena's sister Venus 6-3 4-6 6-4 in a roller-coaster quarter-final on Rod Laver Arena.

The 19-year-old needed a lengthy injury time-out while trailing 1-4 in the second set to have a thigh strain treated but battled back in the third to qualify for her maiden grand slam semi-final. Far from upset by Keys dashing hopes of the first all-Williams grand slam showdown since 2009, the top seed hailed the teenager's emergence as exciting for US tennis.

Williams, who said she'd been battling an energy-sapping virus that is "just getting worse and worse", also knows Keys is a serious threat to her championship hopes.

"What do you want? She's playing great," Williams said.

"Madison has a big serve, a huge forehand. She's improved leaps and bounds, so it's going to be a tough match for me.

"I told her I was really happy that she did well.

"It's good to see another American, another African American, in the semi-finals playing so well.

"Regardless, there's going to be an American in the finals, so that is great.

"It's also great for me and Venus because we know that finally there's other Americans that are constantly playing well and playing better, showing that they want to be the world's greatest."

Keys is the third teenager in three years to make the last four of the Open and said she drew confidence from Sloane Stephens' and Eugenie Bouchard's breakthroughs at Melbourne Park.

"When you see some of your fellow peers doing well, going deep in tournaments, it's inspirational," she said.

"It makes you kind of believe that you can do the same."

The unseeded challenger also credited new coach, 2000 Open champion and former world No 1 Lindsay Davenport, for instilling calm and belief.

No longer does Keys panic in the pressure moments, not even when the world No 35 feared for her tournament during her mini injury crisis on Wednesday.

Keys promised to play through the pain against the world No 1 in what will be the first all-American grand slam semi-final since - as fate would have it - Williams beat Davenport at the 2002 US Open.

"It definitely feels amazing," Keys said. "It's one of those things where you want to feel this way all the time.

"I am very happy and I am very excited, but also not getting too far ahead of myself and being too content where I am. There is more tennis to play."

The winner will take on either Maria Sharapova or 10th seed Ekaterina Makarova, who also play on Thursday. - AAP