Andrew Talansky won the Criterium du Dauphine as Britain's Chris Froome dropped to 12th on the final stage.
Talansky, who got in a 23-man breakaway group, overturned a 39-second deficit on overnight leader Alberto Contador to win the Tour de France warm-up race.
Contador, who had taken the race lead from defending champion Froome on the penultimate stage, finished more than one minute behind American Talansky.
Team Sky's Mikel Nieve won the stage with Britain's Adam Yates in third.
The result lifted Yates, who rides for the Australian Orica GreenEdge team, to an impressive sixth overall.
Nieve's victory was some consolation for the British-based Team Sky at the end of the week-long race that Froome had dominated early on.
The reigning Tour de France champion won the opening time trial in emphatic fashion but admitted a crash on stage six cost him the chance of winning a second successive Dauphine title.
Froome, 29, finished more than five minutes behind his team-mate Nieve after struggling on the ascent to Sunday's summit finish in Courchevel.
"I've felt completely blocked up through my front of quads since the crash and I've not been able to engage the same types of muscles that I used in the earlier stages," he said.
"Contador's shown he's in great form ahead of the Tour though, and we're definitely going to have a battle on our hands in July."
Spaniard Contador had been riding with Froome on the penultimate climb of the day but set off in pursuit of Talansky when he realised that the Briton was incapable of mounting a challenge.
However, Contador failed to catch Talansky on the final ascent and the Garmin-Sharp rider was in tears after securing the title by finishing fourth.
"You put your whole life into something and it can be very hard at times. So moments like this make it all worthwhile," said 25-year-old Talansky after claiming the biggest race win of his career.
"It was a very hard start today, but we saw the opportunity and had to try for it."
The result brings to an end a three-year winning streak by British riders at the Dauphine - Bradley Wiggins won the race in 2011 and 2012, on his way to winning the Tour de France.
The 101st Tour de France starts on 5 July with two stages in Yorkshire and a third from Cambridge to London before the 198 riders transfer to France for the remainder of the three-week race.
Stage eight result:
1. Mikel Nieve (Spa/Team Sky) 3:20:29"
2. Romain Bardet (Fra/AG2R) +3 secs
3. Adam Yates (GB/Orica) +5 secs
4. Andrew Talansky (US/Garmin) +9 secs
5. Jurgen van den Broeck (Bel/Lotto)
6. Tejay van Garderen (US/BMC Racing) +15 secs
7. Wilco Kelderman (Ned/Belkin) +32 secs
8. John Gadret (Fra/Movistar) +36 secs
9. Daniel Navarro (Spa/Cofidis) +41 secs
10. Alberto Contador (Spa/Tinkoff - Saxo) +1:15"
1. Andrew Talansky (US/ Garmin) 31:08:08"
2. Alberto Contador (Spa/Tinkoff - Saxo) +27 secs
3. Jurgen van den Broeck (Bel/Lotto) +35 secs
4. Wilco Kelderman (Ned/Belkin) +43 secs
5. Romain Bardet (Fra/AG2R) +1:20"
6. Adam Yates (GB/Orica) +2:05"
7. Vincenzo Nibali (Ita/Astana) +2:12"
8. Mikel Nieve (Spa/Team Sky) +2:59"
9. Daniel Navarro (Spa/Cofidis) +3:04"
10. Jakob Fuglsang (Den /Astana) +3:17"
12. Chris Froome (GB/Team Sky) + 5:05"