Williams, who has been named on the bench for the Allianz Stadium clash, was rumoured to be in doubt for the game, but trained with his teammates on Wednesday morning.
The New Zealand Rugby World Cup winner underwent surgery on a torn pectoral muscle in November and had his left knee strapped as he was put through his paces.
But Minichiello, who'll lead the team out for the first time since being named captain, said the 27-year-old will definitely play against the Rabbitohs.
"His injury is good, he's got all the ticks from the medical staff," Minichiello said.
"He's trained for the last two weeks, has done all of his contact work.
"He's fit and ready to go and I am looking forward to playing with him."
Williams has not played in the NRL since 2008, when he walked out on Canterbury mid-season to take up a contract with French rugby side Toulon.
His return has dominated the build-up to the new season, but Minichiello said he doesn't expect Williams to be weighed down by the pressure of expectation.
"He's a fantastic player and he has come on board late with us and is working on combinations," he said.
"He'll offer something to us and he'll get better as the season goes on.
"He's a freak of a player and he could have a blinder first game up, who knows."
One player who will miss the game in exciting young back-rower Boyd Cordner.
The 22-year-old was named on an extended bench on Tuesday and has been in outstanding form during the trials.
But damage to the AC joint in his right shoulder which will require surgery at the end of the season, will sideline Cordner who has been tipped as a bolter for NSW this year.
"It's so disappointing to miss round one, especially a game like this, but I should be right for round two," Cordner said.