Peter Horne replaces the injured Finn Russell at fly-half as Scotland aim for their first win in France since 1999 in Saturday's Six Nations encounter.
Russell sustained concussion on club duty, one of four more players to have joined a lengthy casualty list.
Blair Kinghorn starts at full-back with Stuart Hogg also sidelined.
Nick Grigg wins his seventh cap at centre in place of injured Huw Jones, while Magnus Bradbury starts at blind-side flanker with Ryan Wilson also out.
Bradbury, who will play his first Six Nations match on only his fourth Test start and fifth cap, made a successful return from injury for Edinburgh in their victory over Dragons last Friday.
As well as the four enforced changes to the starting line-up, there are four further alterations among the replacements.
Tight-head prop Zander Fagerson, who made his return from a broken ankle in Glasgow's win over Cardiff Blues, takes over from club-mate D'arcy Rae, with Alex Allan replacing fellow Warriors prop Jamie Bhatti as loose-head cover.
Newcastle flanker Gary Graham takes over from Rob Harley, and Glasgow fly-half Adam Hastings and Edinburgh wing Darcy Graham also join the bench with Horne and Kinghorn promoted to the starting XV.
Horne, predominantly an inside centre, has won just eight of his 39 caps at fly-half, six of which came as a replacement.
While the 29-year-old is a regular in the number 10 jersey for Warriors, scoring 18 points in Saturday's win over the Blues, he has not played there for his country since November 2017.
Grigg, 26, will start his second Six Nations match, his first coming against Italy in Rome last March.
Head coach Gregor Townsend, part of the last Scotland side to win in Paris 20 years ago, said: "Injuries create opportunities for others to show what they can do and, throughout the past couple of seasons, we've seen a number of players really step up.
"All of the players coming in started against Argentina in the summer, which ranks as one of our best ever away performances.
"On top of that there is cohesion forged through familiarity at club level - Magnus [Bradbury] in the back row lines up with club-mate Jamie Ritchie, and Pete Horne and Nick Grigg are either side of Sam Johnson in the backs."
France have lost 10 of 13 Tests since Jacques Brunel was appointed head coach in December 2017, and are coming off the back of a record Six Nations defeat by England at Twickenham.
But Townsend is wary of "a very dangerous opponent, combining power, ambition and skill".
"Their individual talent is outstanding and, when they get things right - which has predominantly been in the Six Nations at home - they've played with a real collective spirit and fed off the emotion of the crowd," he added.
"They will certainly be fired up following their loss at Twickenham."
Scotland: Blair Kinghorn (Edinburgh), Tommy Seymour (Glasgow Warriors), Nick Grigg (Glasgow Warriors), Sam Johnson (Glasgow Warriors), Sean Maitland (Saracens), Peter Horne (Glasgow Warriors), Greig Laidlaw (Clermont Auvergne - captain); Allan Dell (Edinburgh), Stuart McInally (Edinburgh - vice-captain), Simon Berghan (Edinburgh), Grant Gilchrist (Edinburgh), Jonny Gray (Glasgow Warriors), Magnus Bradbury (Edinburgh), Jamie Ritchie (Edinburgh), Josh Strauss (Sale Sharks).
Replacements: Fraser Brown (Glasgow Warriors), Alex Allan (Glasgow Warriors), Zander Fagerson (Glasgow Warriors), Ben Toolis (Edinburgh), Gary Graham (Newcastle), Ali Price (Glasgow Warriors), Adam Hastings (Glasgow Warriors), Darcy Graham (Edinburgh).