Scotland saw their title chances ended last weekend when they were thrashed 61-21 by England at Twickenham, but can finish on a positive note against the winless Italians and potentially grab second place in the table for the first time in 17 years.
Ford will win a 107th cap as he replaces Fraser Brown, who moves to the bench, while the only other change among the replacements sees centre Matt Scott take over from Mark Bennett, who has a knee injury.
"The players were frustrated by last weekend but we must take all the learnings from the past years and produce a strong, complete performance to put us in the best possible position to finish in the top-half of the table," coach Vern Cotter said in a statement from Scottish Rugby on Thursday.
Victory, coupled with defeats for Ireland to England and France to Wales, could see Scotland finish in second place in the competition for the first time since 2000, when it was still the Five Nations.
But Cotter has cautioned his side against complacency versus an Italian side that has lost all four games this season and conceded 172 points in the process.
A defeat for Scotland by more than 15 points could also see them drop out of the top eight in the World Rugby Rankings and into the list of third seeds for the 2019 World Cup draw in Kyoto, Japan on May 10.
"Matches between Scotland and Italy have always been tough affairs. We have a lot of respect for them and feel they have been improving throughout the competition," Cotter said.
"They showed in this campaign they can be innovative, so preparation has been key to ensuring we put in a good performance. We have to be ready for anything."
Scotland team:
15-Stuart Hogg, 14-Tommy Seymour, 13-Huw Jones, 12-Alex Dunbar, 11-Tim Visser, 10-Finn Russell, 9-Ali Price, 1-Gordon Reid, 2-Ross Ford, 3-Zander Fagerson, 4-Richie Gray, 5-Jonny Gray, 6-John Barclay (captain), 7-Hamish Watson, 8-Ryan Wilson.
Replacements: 16-Fraser Brown, 17-Allan Dell, 18-Simon Berghan, 19-Tim Swinson, 20-Cornell du Preez, 21-Henry Pyrgos, 22-Duncan Weir, 23-Matt Scott.
(Reporting By Nick Said; Editing by Gareth Jones)
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