Regular skipper Owen Farrell was ruled out of match earlier in the week after picking up a knock in the win over Australia last Saturday.
Lawes will lead the side from the blindside flank with Manu Tuilagi shifting from the wing to replace Farrell at inside centre with Marcus Smith and Henry Slade either side of him in the midfield.
In the front row, Jamie Blamire and Bevan Rodd have been handed starts with Jamie George injured and Joe Marler only deemed ready enough to be involved from bench following a bout of coronavirus.
Eddie Jones has thrown a curve ball on the right wing where outside centre Joe Marchant is picked ahead of specialist Adam Radwan and Max Malins, who has been in free-scoring form for Saracens this season.
Marchant was left out of the original squad for the autumn but a campaign-ending knee injury sustained by Anthony Watson offered a reprieve that culminates in an opportunity against the world champions.
“This is our biggest game of the season and the final game of the autumn campaign and we want to finish with a bang,” Jones said.
“We’ve been really pleased with the preparation this week and how the team has continued to develop over the past month.
“Now we want to put on our best performance this autumn in front of a capacity 82,000 crowd at Twickenham.”