Lawes has played only two club games after 10 weeks out with an ankle injury but goes straight into the starting side in place of George Kruis, who drops out of the squad.
Fullback Mike Brown, who missed the 19-9 defeat in Ireland after suffering concussion in the previous win over Italy, returns to start instead of Alex Goode, who also drops out of the 23.
Flanker Tom Wood is also back among the replacements, as is lock Geoff Parling, for his first taste of the Six Nations since 2013 as England's second-row injury crisis has eased.
Lawes, the team's most destructive tackler and an increasingly important ball carrier, has been a mighty presence for England in the last few years and though Kruis has played well, England should look a tougher prospect with their chief enforcer back in harness.
"It's nice to get Courtney back," Lancaster told reporters on Wednesday.
"He was fantastic in the November internationals, both around the field and in the set piece.
"It's a higher collective level of experience with Geoff and Tom on the bench.
"Bringing players back in as we've done this week, you look around and there is a really high quality squad developing, though it's all about Saturday now."
England could have done with Lawes in the team in Dublin, where their previously expert lineout malfunctioned somewhat, and though his return will be welcomed, they should hardly need him this week.
England have won their last five games against Scotland, who were beaten at home by Italy last time out, and have not lost against them at Twickenham for 32 years.
Another victory should be a given but the hosts will also be looking to rack up the points as their only realistic hope of overhauling Ireland for the title will be via points difference.
Ireland have won all three games and have a 15-point advantage over England ahead of their remaining games away to Wales and Scotland. England finish at home to France in the final game of the championship on March 21.
Lancaster, unsurprisingly, said he and his players would pay no attention to the match in Cardiff, due to finish 30 minutes before the 1700GMT Twickenham kickoff.
"You don't want their heads full of a game they can't control and it will be the same for me," he said.
England: 15-Mike Brown, 14-Anthony Watson, 13-Jonathan Joseph, 12-Luther Burrell, 11-Jack Nowell, 10-George Ford, 9-Ben Youngs; 8-Billy Vunipola, 7-Chris Robshaw (captain), 6-James Haskell, 5-Courtney Lawes, 4-Dave Attwood, 3-Dan Cole, 2-Dylan Hartley, 1-Joe Marler.
Replacements: 16-Tom Youngs, 17-Mako Vunipola, 18-Kieran Brookes, 19-Geoff Parling, 20-Tom Wood, 21-Richard Wigglesworth, 22-Danny Cipriani, 23-Billy Twelvetrees.
(Editing by Justin Palmer and Toby Davis)
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