England have selected a new front row of Joe Marler, Dylan Hartley and David Wilson for Saturday's QBE International against Argentina at Twickenham.
Marler replaces loosehead Mako Vunipola, who started the 20-13 victory over Australia but been sidelined by a knee ligament strain, and Hartley comes in for Tom Youngs at hooker.
Completing the front row overhaul is Wilson's promotion to the starting XV ahead of Dan Cole, who drops to the bench where he is joined by Youngs and Alex Corbisiero.
Corbisiero returns to the 23 after overcoming a knee problem, although he was expected to start the second match of England's autumn series instead of Marler.
The fourth and final change, and the only adjustment to the backline, sees Ben Foden named on the left wing after Marland Yarde and Christian Wade were ruled out through injury.
Yarde has a hip complaint and Wade has incurred a hamstring injury.
"Christian was in contention for a start but his hamstring tightened up in training and unfortunately he hasn't recovered sufficiently in time to be considered," Lancaster said.
"Marland this morning failed a fitness test on a hip injury sustained last weekend so Ben Foden gets his chance with Alex Goode on the bench.
"Ben has had a full week's training on the wing, he is a great finisher and in form so it's a great option for us."
Wade was expected to make his Twickenham debut against Argentina at the expense of Yarde or Chris Ashton until his hamstring tightened up.
Foden fills the left wing slot despite his limited experience in the position with Goode offering back three cover from the bench, which also sees the return of Geoff Parling from mild concussion.
The centre partnership of Billy Twelvetrees and Joel Tomkins remains intact despite a disappointing performance in the autumn opener against Australia.
The biggest surprise, however, is Lancaster's decision to start Marler ahead of Corbisiero against a team that views the scrum as a key weapon.
Corbisiero demolished the Wallabies' set-piece when playing for the British and Irish Lions last summer, although his recent return to fitness may have influenced Lancaster's thinking.
"Joe Marler was excellent off the bench against Australia and merits his opportunity, as does David Wilson, who has been pushing hard for selection," Lancaster said.
"Dylan gets a deserved chance at hooker with Tom Youngs on the bench after the safe arrival of his first child this morning. Rob Webber remains on standby."
England opened a three-match autumn series that concludes against New Zealand on Saturday week with victory over Australia, but the performance left much to be desired.
"The Twickenham crowd was superb against Australia and we were pleased to get the victory, but we know there's more to come from this team and we are looking forward to building on that momentum for this weekend," Lancaster said.
Team to face Argentina:
M Brown (Harlequins); C Ashton (Saracens), J Tomkins (Saracens), B Twelvetrees (Gloucester Rugby), B Foden (Northampton); O Farrell (Saracens), L Dickson (Northampton Saints); J Marler (Harlequins), D Hartley (Northampton Saints), D Wilson (Bath Rugby), J Launchbury (London Wasps), C Lawes (Northampton Saints), T Wood (Northampton Saints), C Robshaw (Harlequins, capt), B Vunipola (Saracens).
Replacements: T Youngs (Leicester Tigers), A Corbisiero (Northampton Saints), D Cole (Leicester Tigers), G Parling (Leicester Tigers), B Morgan (Gloucester Rugby), B Youngs (Leicester Tigers), T Flood (Leicester Tigers), A Goode (Saracens).