Hooker Tom Youngs, brother and Leicester team mate of England scrum-half Ben, is also in line for his first cap having completed a remarkable mastering of his new specialist position three years after switching from centre.
Flanker James Haskell, who impressed in the final game of England's South Africa tour in the summer, is also included in the 32-man squad, as are fit-again Tom Wood and Courtney Lawes, who missed the tour through injury.
Coach Stuart Lancaster has stuck with the Rugby Football Union's policy of not selecting any French-based players for the four Tests which begin against Fiji on November 10 and continue with matches against Australia on November 17, South Africa on November 24 and New Zealand on December 1.
Lancaster was absent from Thursday's news conference for personal reasons but forwards coach Graham Rowntree was on hand to give a ringing endorsement of Vunipola, the latest in a series of radical selections by the coach who replaced Martin Johnson following last year's World Cup.
New Zealand-born Vunipola, still only in his first full Premiership season at Saracens, is the son of former Tonga captain Fe'ao, nephew of two other former Tonga internationals Manu and Elisi
"He's been rewarded for his form in the Premiership, form we just can't ignore. I'm looking for a fault in his game and I can't find one at the moment," said former prop Rowntree.
"He's a dynamic ball carrier but he loves the scrum - and you know how much that turns me on.
"He will definitely feature in the tests and I'm completely comfortable that he will be ready for that step up. I've no doubt that he will make his name."
Monye, 29, made his England debut in 2008 and his first international season was good enough to earn him British and Irish Lions caps in South Africa the following year.
A series of injuries since then knocked him back in the pecking order and his last appearance was in the 2010 Six Nations draw with Scotland.
However, he has been on great form for Harlequins this year and with several other back three contenders, including Ben Foden, injured or returning from injury, he gets another chance.
The November series carries added importance this year as the world rankings at the end of them will be used to base the seedings for the 2015 World Cup.
England are currently fourth, behind the southern hemisphere big guns but only marginally ahead of France, and need to stay there to avoid the likelihood of being placed in the same qualifying pool as New Zealand, South Africa or Australia when they host the tournament.
Rowntree, unsurprisingly, said nobody in the England camp was allowing themselves to look that far ahead.
"If we look after each play, each tackle, each phase, each match then the results and the rankings will look after themselves," he said.
Forwards: Mouritz Botha (Saracens), Dan Cole (Leicester), James Haskell (London Wasps), Phil Dowson (Northampton), Dylan Hartley (Northampton), Tom Johnson (Exeter), Courtney Lawes (Northampton), Joe Marler (Harlequins), Ben Morgan (Gloucester), Tom Palmer (London Wasps), Geoff Parling (Leicester), Chris Robshaw (Harlequins), Mako Vunipola (Saracens), Thomas Waldrom (Leicester), David Wilson (Bath), Tom Wood (Northampton), Tom Youngs (Leicester)
Backs: Anthony Allen (Leicester), Chris Ashton (Saracens), Brad Barritt (Saracens), Mike Brown (Harlequins), Danny Care (Harlequins), Lee Dickson (Northampton), Owen Farrell (Saracens) Toby Flood (Leicester), Alex Goode (Saracens), Jonathan Joseph (London Irish), Ugo Monye (Harlequins), Charlie Sharples (Gloucester), Manusamoa Tuilagi (Leicester), Jordan Turner-Hall (Harlequins), Ben Youngs (Leicester)