The Italians pushed Scotland back in the scrum and stole several of their line-outs, which contributed to the 18-15 defeat in Rome that has put Townsend's side on the back foot ahead of welcoming the "old enemy" to Murrayfield.
Hooker George Turner and prop Nathan McBeth come into the starting XV, while Gregor Brown and Jamie Ritchie have also been added to the back row.
The backline remains unchanged with still no place for rampaging wing Duhan van der Merwe in the match-day 23, despite being a significant thorn in the side of Steve Borthwick's team in the past.
"There are reasons we selected that backline and the bench going into Italy and it's the same reasons going into England," Townsend said.
"We weren't able to play as well as a backline (against Italy) given the weather and opportunities at the start of the game. What the back three did in the kicking battle was excellent and how they have been training is superb so we've backed them again this week."
Scotland have won four of their last five meetings with England, but lost 16-15 when the teams met at Twickenham in last year's championship.
"It's our biggest game of the season and it always has been," Townsend said. "It's even more important on the back of a disappointing defeat."
England started their 2026 championship with a 48-7 home win over Wales.
SCOTLAND (v England)
Jordan, Steyn, Jones, Tuipulotu (capt), Dobie, Russell, White; McBeth, Turner, Z Fagerson, Brown, Cummings, Ritchie, Darge, Dempsey.
Replacements: Cherry, Schoeman, Millar-Mills, Williamson, M Fagerson, Horne, Hastings, Graham.
