Manager Matt Beard told BBC Sport that Williams and Nigeria striker Asisat Oshoala would miss "a couple of months" with hamstring and knee problems.
Defender Satara Murray (also hamstring) is expected to be out of action for about six weeks.
"It's a big blow," said Beard.
"It's the spine of your team - your central midfielder, your centre-back and your centre-forward - but it's one of those things."
The players were all hurt during Saturday's WSL 1 defeat by Notts County and did not feature in Thursday's 2-0 Continental Tyres Cup victory against Everton.
Williams played in all seven of England's matches at the recent World Cup, but Beard said her injury was not caused by returning to league action too soon following the tournament in Canada.
"It was an impact injury," he said. "Unfortunately as she's tried to win the ball, her leg's completely hyperextended, which has caused the injury."
Liverpool are the reigning Women's Super League One champions but are currently only sixth in the table after a disappointing start to the season.
With the league concluding in October, Beard admitted that the new injuries would make defending their title even more difficult.
"They're important players to us but it's going to give maybe one or two of the younger players an opportunity," he continued.
"We'll do as much as we can, while we're still involved in everything mathematically, to finish as high as we can."
Beard also told BBC Sport that he did not think he would be in a position to make emergency loan signings to cover for the injured players.
Three Liverpool Ladies players, including England midfielder Fara Williams, are set to miss the majority of the club's remaining games this season after picking up injuries.