Impey is the first South African to wear the leader's jersey but he faces a tough challenge on the 205.5-km leg from Montpellier to Albi, which features a sharp six-kilometre category 2 climb up Col de la Croix de Mounis.
VIDEO: Impey celebrates behind-the-scenes
The stage is a precursor to an even tougher weekend in the Pyrenees, where race favorites like Chris Froome and Alberto Contador are likely to attack.
American veteran Christian Vande Velde was caught up in a crash early in Friday's stage and had to pull out of the race.
Norwegian sprinter Edvald Boasson Hagen, Colombian rider Nairo Quintana and Michael Schar of Switzerland were among those to also fall about 111 kilometers into the stage.
They rejoined the race, but the 37-year-old Vande Velde - who hurt his back in a crash earlier in the race - was unable to continue.
There have been several multi-rider crashes in what has been a nervy Tour so far, even though the course itinerary has not been to blame.
On the first stage, there was a big crash close to the end after Tour organizers caused panic in the peloton by changing the designated finish line because a team bus was stuck on the line, before changing their minds again moments later.
The fifth stage featured two separate crashes, the second right on the finish line, and the sixth stage claimed British sprinter Mark Cavendish among the fallen.