The 27-year-old from the Isle of Man operated primarily on his own in the finale and showed his supreme bike handling ability on Monday's 207.5-kilometre second stage from Vise to Tournai to win ahead of Andre Greipel (Lotto-Belisol) and Matt Goss (Orica-GreenEdge).
With Team Sky's priority Bradley Wiggins' bid for overall victory and the Olympic Games on July 28 Cavendish's main focus, it is anticipated the points classification's green jersey will be on the shoulders of another rider come Paris on July 22.
But Cavendish, now sixth behind Eddy Merckx on the list of all-time Tour stage winners and one stage behind Lance Armstrong, appears unwilling to give up the prize without a fight.
Fabian Cancellara (RadioShack-Nissan) retained the race leader's yellow jersey, with Wiggins second overall, still 10 seconds clear of defending champion Cadel Evans (BMC Racing). All three finished in the main bunch.
Christophe Kern (Europcar), Michael Morkov (Saxo Bank-Tinkoff Bank) and Anthony Roux (FDJ-Bigmat) formed the day's three-man break which had little chance of survival on a route made for the fast men of the peloton.
The intermediate sprint came 54.5km from the finish, with Kern, Roux and Morkov riding across without contesting the race for the line, leaving the first rider of the peloton chasing 13 points.
Cavendish was alone for Team Sky and crossed behind former HTC-Highroad team-mates Goss and Mark Renshaw (Rabobank) to claim nine points.
The gap to the escapees was kept to under three minutes and Roux launched a solo attack as his two fellow escapees were swept up with around 25km to go on a straight run-in into Tournai.
With a full-speed peloton in pursuit, Roux was caught with just under 15km remaining.
The sprinters' teams lined up, while Evans' BMC Racing squad were also prominent at the front, with Wiggins staying out of trouble alongside.
Cavendish's sprint rival Marcel Kittel (Argos-Shimano), though, was at the back of the peloton due to illness.
The tempo was high as the peloton negotiated a technical and tight conclusion, including two roundabouts and a narrowing section of road.
Lotto-Belisol moved to the front with 1.5km to go, but all the main protagonists were present as Cavendish tucked in behind Greipel.
With his team-mates primarily assigned to support Wiggins, Cavendish, who had early support from Bernhard Eisel and Edvald Boasson Hagen, had to freestyle from wheel-to-wheel in the finale before timing his move to perfection, rounding Greipel with 200metres to go and winning the dash for the line to add to his formidable total of stage wins.
Watch: Cavendish takes 21st win on Stage two... More Videos
It was the first time Cavendish has won a stage of the Tour outside France.
Cavendish talked down his prospects of retaining the green jersey in a year where both his and the team's priorities lie elsewhere but vowed to make the most of what chances he has.
"I had to leave it a little bit late but I should have gone earlier...I really had to lunge for the line," he told British Eurosport.
"I'm not really chasing (the green jersey) this year. I'll keep it in the back of my mind and go for every opportunity but I'm not going to put myself in the ground for it.
"It's not possible to chase the green jersey alone so I'm just trying to get the stages and then see.
"I'll go for the intermediates but I'm not going to chase down breaks to go for it. It's about minimising points lost really."
Assessing the stage itself, a typically tough early day in the Tour, he added: "It was so hectic. If it had just been sprinters it would have been okay but every type of climber and GC (general classification) rider was at the finish.
"I knew it would be difficult, dangerous and hectic here but I came in without any pressure. it was just about being plucky about it.
"I knew the finish and knew there was a headwind, so I knew you could come from behind."