The 26-year-old Glasgow centre made his debut against Italy in a World Cup warm-up match last year before being dropped from Gregor Townsend's squad for the tournament in France.
Regular midfielder Sione Tuipulotu's recent injury enabled Cameron Redpath to make a rare start in last week's damaging 31-29 defeat away to Italy.
But McDowall, in good form for Glasgow, has been chosen ahead of Redpath as Scotland look to end a tournament in which they have already defeated Wales and England on a high.
In the other change to the team that started in Rome, first-choice scrum-half Ben White returns in place of George Horne after the Toulon number nine was rested for the Stadio Olimpico clash with the Azzurri.
Scotland will be bidding for their first Triple Crown - when one of England, Scotland, Ireland and Wales beats each of those other teams in a single championship season - since 1990.
But they have lost their past nine matches against Ireland in all competitions, with their most recent reverse a 36-14 pool defeat at last year's World Cup in France.
Ireland, denied back-to-back Grand Slams in a dramatic 23-22 loss to England at Twickenham last weekend, need only a losing bonus point on Saturday to retain their Six Nations title.
Scotland (15-1)
Blair Kinghorn; Kyle Steyn, Huw Jones, Stafford McDowall, Duhan van der Merwe; Finn Russell (co-capt), Ben White; Jack Dempsey, Rory Darge (co-capt), Andy Christie; Scott Cummings, Grant Gilchrist; Zander Fagerson, George Turner, Pierre Schoeman
Replacements: Ewan Ashman, Rory Sutherland, Elliot Millar-Mills, Sam Skinner, Matt Fagerson, George Horne, Cameron Redpath, Kyle Rowe
Coach: Gregor Townsend (SCO)