The Omega Pharma-Lotto rider, who finished last year's Tour de France in fifth place overall, attacked with less than five kms to go to beat Spaniard Joaquim Rodriguez of the Katusha team after 144km from Albertville.
Australian Cadel Evans finished third for the BMC team.
Kazah Alexandre Vinokourov (Astana) claimed the overall lead while several Tour de France hopefuls, who use the Dauphine as a preparation for next month's race, were unable to follow the pace in the final 10km ascent to St Pierre de Chartreuse.
Van den Broeck broke away to catch Thomas Voeckler midway through the climb and did not even look back when he went past the French champion.
"It's my first big win, it's good for my morale," Van den Broeck told French TV channel France 3.
"I'm just back from five weeks training in altitude and my legs were not very good."
It was enough, though, to resist Rodriguez's comeback as the Spaniard finished six seconds behind, with former world champion Evans seven seconds off the pace.
Briton Bradley Wiggins took fourth place 11 seconds adrift of Van den Broeck.
Italian Ivan Basso, the 2010 Giro champion, finished three minutes nine seconds off the pace as he realised his build-up to the Tour would be all but a stroll in the park.
Tuesday's stage is a 179km ride from Voiron to Lyon, ending with a 1.4km climb at an average gradient of 4.8 percent.
The Criterium du Dauphine ends on Sunday, three weeks before the start of the Tour de France on July 2.
Results and provisional standings:
1.Jurgen Van den Broeck (Belgium/Omega Pharma-Lotto) 3h 36m 42s
2. Joaquim Rodriguez (Spain / Katusha) +6"
3. Cadel Evans (Australia / BMC Racing) +7"
4. Alexandre Vinokourov (Kazakhstan / Astana)
5. Nicolas Roche (Ireland / AG2R)
6. Edvald Boasson Hagen (Norway / Team Sky)
7. Thibaut Pinot (France / FDJ) +13"
8. Rob Ruygh (Netherlands / Vacansoleil)
9. Thomas Voeckler (France / Europcar) +15"
10. Janez Brajkovic (Slovenia / RadioShack)
Overall standings
1. Alexandre Vinokourov (Kazakhstan / Astana) 3hrs 43mins 09s
2. Jurgen Van den Broeck (Belgium / Omega Pharma - Lotto) +5"
3. Cadel Evans (Australia / BMC Racing) +7"
4. Bradley Wiggins (Britain / Team Sky) +11"
5. Edvald Boasson Hagen (Norway / Team Sky) +13"