American Lance Armstrong ruled himself out of going for an eighth Tour de France title after crashes saw him finish Sunday's action-packed eighth stage almost 12 minutes adrift.
Schleck, the Saxo Bank rider who finished second in last year's Tour, out-sprinted Euskaltel's Samuel Sanchez for the stage win after the duo broke 1km from the summit finish line.
World champion Evans and reigning Tour de France champion Alberto Contador finished in a group of nine riders 10sec later.
But the first day's racing in the high mountains proved to be a disaster for seven-time Tour winner Armstrong, who crossed the line 11:45 adrift of Schleck's pace.
The American fell twice during the stage and lost ground from the col de la Ramaz, the first major climb of the Tour. He now stands 39th in the overall standings, 13:26 off Evans.
"My Tour is over," said Armstrong. "But I will stay in the race.
I will enjoy it, I'll try and take some pleasure out of it, to support the team. I'm not complaining." The 38-year-old fell first just after the start from Les Rousses and then a second time on the approach to the col de la Ramaz.
"I've had a bad day, a very bad day. At the start, it was going okay, I felt strong.
"And then came the roundabout before the col de la Ramaz. I clipped a pedal and then my tyre rolled off and the next thing I was rolling along the ground at 60-65 kph. "It's already hard to come back, hard on the body."
Eighth stage results:
1. Andy Schleck, Luxembourg, Team Saxo Bank, 4 hours, 54 minutes, 11 seconds.
2. Samuel Sanchez, Spain, Euskaltel-Euskadi, same time.
3. Robert Gesink, Netherlands, Rabobank, 10 seconds behind.
4. Roman Kreuziger, Czech Republic, Liquigas-Doimo, same time.
5. Alberto Contador, Spain, Astana, same time.
6. Cadel Evans, Australia, BMC Racing Team, same time.
7. Jurgen Van Den Broeck, Belgium, Omega Pharma-Lotto, same time.
8. Levi Leipheimer, United States, Team RadioShack, same time.
9. Ivan Basso, Italy, Liquigas-Doimo, same time.
10. Denis Menchov, Russia, Rabobank, same time.
11. Carlos Sastre, Spain, Cervelo Test Team, same time.
12. Michael Rogers, Australia, Team HTC-Columbia, :20.
13. Joaquin Rodriguez, Spain, Katusha, :39.
14. Ryder Hesjedel, Canada, Garmin-Transitions, 1:14.
15. Kevin De Weert, Belgium, Quick Step, same time.
16. Andreas Kloeden, Germany, Team RadioShack, same time.
17. Ruben Plaza, Spain, Caisse d'Epargne, 1:37.
18. Thomas Lovkvist, Sweden, Sky Pro Cycling, 1:45.
19. Bradley Wiggins, Britain, Sky Pro Cycling, same time.
20. Anthony Charteau, France, Bbox Bouygues Telecom, 2:05.
Also
27. Alexandre Vinokourov, Kazakhstan, Astana, 2:23.
60. Sylvain Chavanel, France, Quick Step, 11:40.
61. Lance Armstrong, United States, Team RadioShack, 11:45.