Saracens prop Vunipola has emerged as the likely replacement for Alex Corbisiero, who is not due to return to action from a knee injury until mid-November.
Lancaster, who names his squad on Thursday, will also announce replacements for Ben Foden, Tom Croft and Rob Webber, who are all out of England's Tests against Fiji, Australia, South Africa and New Zealand.
Leicester hooker Tom Youngs, who toured South Africa with England in the summer, is set to be promoted into the senior squad as Dylan Hartley's immediate understudy for the four-Test series.
Ugo Monye's form for Harlequins has caught Lancaster's eye and he is due to fill the back three place vacated when Foden damaged ankle ligaments playing for Northampton.
England also need to replace Croft, with the leading back-row options being Joe Launchbury, James Haskell and Carl Fearns.
Lancaster has already made one change to the original elite squad he announced in July, replacing retired prop Matt Stevens with Bath's David Wilson.
Wilson's selection opened the way for Vunipola to be named in the England Saxons - but the 21-year-old is set to be promoted again after an impressive start to his first full-season in the Premiership.
The 20-stone loose-head prop was born in New Zealand. His father, Fe'ao Vunipola, won 32 caps for Tonga and played at the 1995 and 1999 World Cups.
Although he qualifies for Wales after the family relocated when Fe'ao signed for Pontypool in 1998, Vunipola has played for England Under-18s and the Under-20s.
Vunipola missed the whole of last season through injury after moving from Bristol to Saracens, but he has already made a big impression this year.
"He has risen to every challenge he has had so far," said Saracens director of rugby Mark McCall.
"He has played some big games for us and is an outstanding young talent.
"Corbisiero's injury opens the door for Mako. But Mako is more than ready, he is as good a rugby-playing loosehead as I have come across."
England's autumn campaign is a daunting one but Lancaster is refusing to set any target other than a clean sweep. He believes that to aim for anything less would be to accept defeat.
"Our goal is to win them all," Lancaster said.
"Teams take time to evolve but we hope to build on the momentum of the South Africa tour. The future is hugely exciting and the players are buzzing about being here."
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