Henry Slade’s absence from the 33 players who will depart for France next month provided the biggest selection shock, but close behind was the omission of Alex Dombrandt.
England’s first-choice number eight throughout the Six Nations failed to make the required impression in Saturday’s final trial match against Wales, which ended in a tame 20-9 defeat.
Vunipola is the only option with expertise in the position but the 30-year-old Saracen has been sidelined since mid-April after undergoing two knee surgeries and has yet to play under Borthwick.
Borthwick has witnessed enough, however, to believe he can make an impression on his third World Cup.
“Billy has been fantastic in this training camp. I’ve seen just how hard he’s worked to come back from his injury,” England’s head coach said.
“He looks in great shape and is the fittest I’ve ever seen him. His experience will add to this squad.
“I’ve had the opportunity to work with him for a long period of time now and the opportunity to understand what the team needs.”
Taking a second specialist number eight to the tournament is seen by Borthwick as a luxury England cannot afford.
Instead, he has stocked his back-row contingent with players who can cover multiple positions with Lewis Ludlam, Ben Earl and Tom Curry alternatives if Vunipola becomes unavailable.
“Alex has done really well and has trained well. He’s a very, very good player,” Borthwick said.
“There’s a lot of competition in the back row and there’s also flexibility around those positions.
“Lewis Ludlam has the ability to play six, seven and eight. Ben Earl has the ability to play seven and eight. Curry seven, eight and six.
“There’s a lot of flexibility there and for me it’s about making the decision on the right combination and ultimately that’s what it’s come down to.”
Slade has lost out to Joe Marchant, who alongside Ludlam was one of only two players to emerge from the wreckage at the Principality Stadium on Saturday with his reputation enhanced.
Borthwick indicated that the decision to take three front line fly-halves in Owen Farrell, George Ford and Marcus Smith to ensure there is adequate cover in the event of injury or suspension ultimately cost the Exeter centre.
“Henry has been excellent throughout the training camps,” said Borthwick, who repeatedly declined to say if he believed England can win the World Cup.
“I decided we’d have three players in key positions – front row, scrum-half, fly-half – for the obvious reasons. That means in the other areas of the team you need to have positional flexibility.
“Henry was clearly disappointed but the message to all the players who haven’t been selected is to be ready to come into the squad.
“We know there will be changes. Past World Cups show there are always bumps and bruises and there will be changes.”
Other big names to miss out are wings Jonny May and Joe Cokanasiga, both of whom played in the World Cup four years ago.
Rookie Leicester duo Ollie Chessum and George Martin are present, while inexperienced hookers Theo Dan and Jack Walker supply cover for veteran Jamie George.
Henry Arundell offers X-factor in the threequarters with his selection coming at the expense of Cokanasiga.
Courtney Lawes, Dan Cole and Ben Youngs will be appearing at their fourth World Cups in a squad that contains more than 1,400 caps and is comprised of 19 forwards and 14 backs.
Farrell was confirmed as captain last month with Lawes and Ellis Genge acting as his vice skippers.