The Belgian squad, including in their ranks the reigning world individual time trial champion Tony Martin, completed the 16.9km route from San Vincenzo to Donoratico in 19:24 - an average speed of 52.268 km/h in wet conditions in Tuscany.
Team Movistar was next, 11 seconds slower, with Cadel Evans's BMC squad a further five seconds back in third.
Over the same route last year, Orica-GreenEdge set the winning time of 18:41, 17 seconds faster than Fabian Cancellara’s RadioShack-Nissan.
But the Australian squad had to settle for sixth this year in 19:48 behind Cannondale (19:42) and the Astana squad of defending champion Vincenzo Nibali (19:44) while RadioShack were back in tenth in 20:00 behind Chris Froome's Team Sky (19:49), Alberto Contador's Saxo-Tinkoff (19:53) and Lampre (19:59).
MTN-Qhubeka, who became the first African team ever to start a UCI World Tour race, came home in 20:24.
Cavendish said: “It was raining when we trained yesterday and this morning, but the guys didn’t care about the weather. They wanted to keep practicing and practicing and get it right, and they really did. It was nice to be part of it.
"It’s a misconception that the five who crossed the finish line together were the strongest. Tony rode away from us on the climb. Geert Steegmans waited for us and led the rest of the team back to him. He had one of the best rides today.
"It was planned I’d cross the line first. With hindsight it would have been better to let Tony [Martin] cross first because he did about half of it on his own today. He’ll probably get the jersey later in the week. “I expect a pretty straightforward sprint tomorrow. We’ll be riding to keep the jersey, although I hope it’s not left to us to ride the whole day.”
The World Tour race has a star-studded start list which includes the winners of 11 Grand Tours, 14 one-day monuments, 12 World Championships, two Olympic gold medals on the road and three Olympic track champions.
Stage 1: Wednesday 06/03: San Vincenzo – Donoratico (16.9km)
Stage 2: Thursday 07/03: San Vincenzo – Indicatore (232km)
Stage 3: Friday 08/03: Indicatore – Narni Scalo (190km)
Stage 4: Saturday 09/03: Narni – Prati di Tivo (173km)
Stage 5: Sunday 10/03: Ortona – Chieti (230km)
Stage 6: Monday 11/03: Porto Sant’Elpidio – Porto Sant’Elpidio (209km)
Stage 7: Tuesday 12/03: San Benedetto del Tronto – San Benedetto del Tronto (9.2km)
Most wins - Riders
6 Roger De Vlaeminck (BEL) 1972, 1973, 1974, 1975, 1976, 1977
2 Francesco Moser (ITA) 1980, 1981
2 Giuseppe Saronni (ITA) 1978, 1982
2 Toni Rominger (SUI) 1989, 1990
2 Rolf Sørensen (DEN) 1987, 1992
Most wins - Countries
Last 10 podiums
2012: Vincenzo Nibali (ITA) Chris Horner (USA) Roman Kreuziger (CZE)
2011: Cadel Evans (AUS) Robert Gesink (NED) Michele Scarponi (ITA)
2010: Stefano Garzelli (ITA) Michele Scarponi (ITA) Cadel Evans (AUS)
2009: Michele Scarponi (ITA) Stefano Garzelli (ITA) Andreas Klöden (GER)
2008: Fabian Cancellara (SUI) Enrico Gasparotto (ITA) Thomas Löfkvist (SWE)
2007: Andreas Klöden (GER) Kim Kirchen (LUX) Alexandr Vinokurov (KAZ)
2006: Thomas Dekker (NED) Jörg Jaksche (GER) Alessandro Ballan (ITA)
2005: Óscar Freire (ESP) Alessandro Petacchi (ITA) Fabrizio Guidi (ITA)
2004: Paolo Bettini (ITA) Óscar Freire (ESP) Erik Zabel (GER)
2003: Filippo Pozzato (ITA) Danilo Di Luca (ITA) Ruggero Marzoli (ITA)