Konta eased past Russia’s Ekaterina Makarova 6-1 6-4 on Margaret Court Arena and now faces the fiercest opponent in the game for a place in the last four.
Williams is by a distance the most decorated player in the tournament, standing three wins away from a seventh Melbourne triumph and an Open era record 23rd grand slam title.
But Konta is the player in form, hoping to extend a nine-match unbeaten streak that included thrashing world number three Agnieszka Radwanska en route to winning the Sydney International title.
The British number one possesses the weapons to hurt Williams - her demon serve, driving backhand and quickness across the baseline - but ousting the American is as much a mental battle as a technical one.
“I believe in my own ability. I believe in the good things that I bring to the court, and I believe in my ability to fight till the very end,” Konta said.
“Now, there’s that and then there’s also an opponent out there, and this one’s going to be Serena Williams.
“I think it’s about me going out there and doing what I want to do against her and it will be about just staying focused on that.
“If that brings me good things on that day and if that puts me in a position to come through, then that’s great.
“But I’ve got to focus on the work and not think of whether I can or cannot beat her.”
Konta knocked Serena’s sister Venus out in the first round here 12 months ago and went on to face eventual champion Angelique Kerber in the semi-final.
Since then, she has played 11 matches against top-10 opponents and beaten seven of them, including Radwanska, Madison Keys, Karolina Pliskova and Venus Williams again.
Serena, however, represents another step up and Konta admits only when out on court will she know if she can separate the player from the success.
“I guess I need to be on court with her and against her first, to see how I deal with things,” Konta said.
“I have been fortunate enough that I have played her sister a few times and I think she’s just as incredible in what she’s achieved in the sport.
“I have played, over the last year and a half, quite a few grand slam champions and some former world number ones.
“So I think I have prepared myself as much as possible to play a competitor like Serena.”
When Williams beat Maria Sharapova to win her last Australian Open title in 2015, Konta was stewing over a defeat in the first round of qualifying to an opponent ranked 141st in the world.
She now sits ninth in the rankings, the key to her transformation a new-found resilience under pressure. So what if she is serving for the match against Williams?
“You have got to put things in perspective,” Konta said.
“When you see a glimmer of what you have dreamed of as a little girl or what you hoped for, what you’ve worked so hard for, it can feel kind of like an all-or-nothing moment or ‘what if I never get this chance again?’
“I think that’s where you have also got to have a good perspective on things and you’ve got to keep the simple things in mind of what’s important to you.
“Are you healthy? Is your family healthy? Do you have people around you that you love? Do you have people around you that love you?
“I know it might sound really mundane and simple but I guess you’ve got to go back to things that have got substance, and then in the end just trust in the work that you do.”