The Australian confirmed on Wednesday she had torn her ACL while playing in a Tokyo WTA event.
Saville suffered the same knee injury in 2013 and had only this year fully recovered from a debilitating foot issue that she'd battled for two years to surge back into the world's top 60.
"Torn ACL. 2013 flashbacks," she tweeted.
"Don't worry about me by the way. I feel bad that everyone is so worried. I'm okay, I promise. It's just shit luck."
Saville was injured in her first-round contest with Naomi Osaka.
In just the second game, Saville yelled in pain after playing a short forehand and collapsed to the court in distress clutching her left knee.
She was able to walk away after some treatment but did not risk continuing, shaking hands with Osaka after only 11 points.
Saville had moved to No.55 in the world after starting the season ranked 419th, reaching her first WTA final in almost five years in August.
The 28-year-old now faces another long recovery period that will see her miss the Australian Open.
Osaka, who ended a four-match losing run in unfortunate fashion, has had her own injury problems this year with Achilles and back issues and the former world No.1 had not won a match since the beginning of August.
"I just wanted to wish you the best," the current world No.48 said in a social media video message to Saville.
"I just want to let you know you're one of the funniest people on the tour, and I still remember all the nice things that you said to me at the French [Open] this year. I want you to know that I'm wishing you the best. I hope that it's not a major injury at all and you'll bounce back, because I know that's what you're good at."
In the opening match of Wednesday's schedule, third seed and world No.12 Garbine Muguruza of Spain enjoyed a 6-4 6-2 win over Greek Despina Papamichail.
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