Stuart Hogg will start the match at stand-off in place of Finn Russell who has been ruled out with a head knock.
The Scotland captain played the last 20 minutes of the defeat against Ireland last Sunday in the fly-half role.
He is partnered at half-back by Scott Steele who comes into the side for his first Scotland start. Regular scrum-half Ali Price is named among the replacements.
Hogg's switch to 10 means Sean Maitland goes to full-back, with Darcy Graham taking Maitland's wing berth.
There is also a change at outside centre, with Huw Jones preferred to Chris Harris. Jones scored a try as a second-half substitute in the 27-24 loss to the Irish.
In the forwards, there is a new second-row pairing with Sam Skinner and Grant Gilchrist replacing the injured Scott Cummings and Jonny Gray.
There are also two changes in the front row. Hooker David Cherry will make his first start for Scotland, with George Turner dropping to the bench.
Zander Fagerson is back at tighthead prop after serving his suspension following his red card against Wales. WP Nel drops out of the squad.
The Scotland v Italy match kicks off at 2.15pm, and is live on BBC1.
A message from the Editor:
Get a year of unlimited access to all The Scotsman's sport coverage without the need for a full subscription. Expert analysis of the biggest games, exclusive interviews, live blogs, transfer news and 70 per cent fewer ads on Scotsman.com - all for less than £1 a week. Subscribe to us today
. EDINBURGH, SCOTLAND - NOVEMBER 10: Scotland head coach Gregor Townsend during Scotland rugby training at Oriam on November 10, 2020, in Edinburgh, Scotland (Photo by Craig Williamson / SNS Group)
Scotland head coach Gregor Townsend has named his starting side to face Italy in this Saturday's Six Nations clash at Murrayfield. (Photo by Craig Williamson / SNS Group) Photo: Craig Williamson - SNS Group / SRU
. Rory Sutherland
The Edinburgh prop starts at loosehead. Photo: Brendan Moran - SNS Group
1. Rory Sutherland
The Edinburgh prop starts at loosehead. Photo: Brendan Moran - SNS Group
2. David Cherry
Edinburgh hooker replaces George Turner to make his first start for Scotland. Photo: Ross Parker - SNS Group
3. Zander Fagerson
Glasgow Warriors tighthead returns from suspension and replaces WP Nel. Photo: Craig Williamson - SNS Group / SRU
4. Sam Skinner
Exeter Chiefs man comes into the second row following injuries to Jonny Gray and Scott Cummings. Photo: Paul Devlin - SNS Group