The Omega Pharma-Quick Step sprinter was expertly launched by team-mate Gert Steegmans in the closing straight before winning by a bike length ahead of rivals Elia Viviani (Cannondale) and Matt Goss (Orica-GreenEdge).
It was Cavendish's twelfth individual Giro stage win of his career - and his second on the 2013 race following the opening day victory in Naples. The 27-year-old also moves back into the red jersey at the top of the points classification.
Overnight race leader Luca Paolini (Katusha) finished safely in the peloton to retain his maglia rosa. The Italian leads Rigoberto Uran (Team Sky) by 17 seconds and Benat Intxausti (Movistar) by 26 seconds.
After his ninth scalp of the season, Cavendish was quick to praise his team-mates for a near-flawless day in the saddle.
"It was unbelievable. I'm so happy," said Cavendish after exchanging a series of hugs with his OPQS colleagues. "We had no problems today. Everything went well. It was beautiful. Gert Steegmans at his best is one of the best lead-out men ever."
The former world champion showed his poetic side with a well-crafted simile: "Imagine a big car - the team are all the important bits and the engine. I'm just the last bit at the end - the exhaust - the bit that makes the most noise."
Cavendish also had a message for a former Quick Step rider sorely missed by friends, family and the world of cycling alike.
"I'd like to dedicate this win to Wouter Weylandt. It's two years ago today since his tragic death," he said, referring to the Belgian rider who suffered a fatal fall on the descent of the Passo del Bocco on stage three of the 2011 Giro.
If ever there was a stage with Cavendish's name on it - this was it. The short 169km ride along the Adriatic Coast and through the flat countryside of Puglia concluded with two laps of a 16km circuit and a pancake flat finale.
Two Australians - the attacking Cameron Wurf (Cannondale) and young track specialist Jack Bobridge (Blanco) - broke clear of the pack early on and built up a maximum lead of six and a half minutes.
With Wurf in the break, the Cannondale team of Italian sprinter Viviani were under no obligation to lead the chase - but they were nevertheless fairly active on the front of the peloton as their man nipped ahead of Cavendish on two occasions to take third place behind the escapees in the intermediate sprints.
With points from the finish taken into account, Viviani now trails Cavendish by six points in the standings in what is now looking to be a two-horse race.
Britain's Bradley Wiggins (Team Sky) had a scare after being caught up by a large pile-up which caused half the peloton to come to a complete standstill on the first of two laps 32 kilometres from the finish.
The Tour de France champion was returning to the back of the peloton after picking up a puncture when the incident occurred. With the crash barriers on the side of the road and the heap of mangled bikes and bodies forming a barricade on the road, Wiggins and four Sky team-mates could do nothing but wait until an opening emerged.
Luckily for Wiggins several other GC contenders were involved in the split - including Italian favourite Vincenzo Nibali of Astana and compatriot Michele Scarponi of Lampre-Merida.
As such, the pace slowed on the front of the main pack until order was restored with 22km left to ride.
Inside the final five kilometres two riders - Manuele Boaro (Saxo Bank-Tinkoff) and Pim Ligthart (Vacansoleil-DCM) - were both thwarted after audacious solo attempts.
The scene was set for a sprint battle royale - and the main protagonists did not disappoint.
The Argos Shimano team of Wednesday's winner John Degenkolb, however, made a hash of their tactics, launching their man too early and disappearing without a trace.
Instead, Belgian powerhouse Steegmans ushered Cavendish through with aplomb - although it wasn't a pretty affair. As much as OPQS got their tactics right on Thursday, they are no HTC. And they certainly benefited from the disarray among other teams.
French national champion Nacer Bouhanni (FDJ) found himself boxed in by the barriers on the left while Italian Mattia Gavazzi (Androni-Giocattoli) appeared to propel himself past South African Robbie Hunter (Garmin-Sharp) by using his arms to pull back his opponent.
Hunter and Gavazzi almost came to blows in the finish area - and the race commissaires will no doubt have a look at replays and discipline the Italian accordingly.
There was no doubt about the win, however. From the moment Steegmans pulled away there was no doubt that Cavendish was going to double his tally on the 96th edition of the Corsa Rosa.
Viviani and Goss both did their best to get in the mix - but in the end they were sprinting for second place. Bouhanni crossed the line in fourth and slammed the handlebars in disgust after what was an extremely edgy affair.
The Giro continues on Friday with the hilly 177km stage seven through the Abruzzo region. With four categorised climbs on the menu, the testing stage from Marina Di San Salvo to Pescara on the Adriatic Coast will be the first major rendez-vous for the big race favourites.