Head coach Eddie Jones expects the two first-choice internationals to benefit from the opportunity to work on their conditioning.
"We named a training squad of 45 and we were always going to have a look at each player separately and whether or not it is in their best interests to tour," Jones said in a statement.
"Bill has played more than 550 minutes of Test rugby already this season and with a groin injury at the start of the year he didn't really get a good off-season.
"He needs a break from playing and the chance to work on an extensive strength and conditioning program leading into next year."
Jones said Mortlock needed time to regain full fitness.
"Stirling is a slightly different proposition, missing four Super 12 matches through injury and three Tests," Jones said.
"The break will also give him the opportunity to work hard on his strength and speed."
Meanwhile, recent Test debutant Alex Kanaar, who was suspended from all forms of rugby for three months on Monday for stamping, will be replaced in the now 42-man training squad by fellow Australia 'A' lock, Adam Wallace-Harrison, who started against the Junior All Blacks in Sydney earlier this year.
The 30-strong tour squad to play Tests against France, England, Wales and Ireland will be named on Tuesday October 11.