England bench Vunipola, Tuilagi and Youngs for Japan Test
Sam Simmonds has replaced Vunipola as the starting No 8, with Guy Porter taking over from Tuilagi at outside centre.
Jack van Poortvliet, who scored a try shortly after coming off the bench in place of Youngs, starts at scrum-half.
In all Jones has made five changes to his starting XV for England's second match of a November programme that also features Tests against New Zealand and world champions South Africa.
Jonny May has overcome an elbow problem to replace Joe Cokanasiga, even though his fellow wing scored England's opening try against Argentina.
Up front, South Africa-born lock David Ribbans makes his Test debut in place of Northampton team-mate Alex Coles, who won his first cap last weekend.
Jamie George has recovered from a foot injury to provide cover for starting hooker Luke Cowan-Dickie.
"We've worked hard this week to improve on last week's performance," said Jones.
"We've taken a good look at our preparation and we are happy with our position going into the game.
"We've made a few changes to the side as we play these four games in November. In particular with Manu we are balancing his workload."
Jones, Japan's coach when they defeated the Springboks in a stunning upset during the 2015 World Cup in England, added: "Japan are a very good and intriguing side.
"They play a unique type of rugby based on continuity and team cohesion and we'll have to be at our best against them at Twickenham on Saturday."
Team (15-1)
Freddie Steward; Jack Nowell, Guy Porter, Owen Farrell (capt), Jonny May; Marcus Smith, Jack van Poortvliet; Sam Simmonds, Tom Curry, Maro Itoje; Jonny Hill, David Ribbans; Kyle Sinckler, Luke Cowan-Dickie, Ellis Genge
Replacements: Jamie George, Mako Vunipola, Joe Heyes, Alex Coles, Billy Vunipola, Ben Youngs, Henry Slade, Manu Tuilagi
Coach: Eddie Jones (AUS)