Kittel won three consecutive editions of the Belgian classic between 2012 and 2014, missing the race last year, but returned to take victory in the sprint finish in Schoten on Wednesday.
The German's Etixx team took control on the front of the peloton in final few kilometres of the race, despite the proximity of teams for André Greipel (Lotto-Soudal) and defending champion Alexander Kristoff (Katusha).
Cavendish, who looked to have burned through his teammates earlier in the race as the riders took on three 16km finishing circuits, stuck to the wheel of Kittel as his team drove on the front.
Once Kittel was dropped off by his team in final few hundred metres, it was clear that it was a straight shoot-out between Cavendish and Kittel.
The latter launched his sprint first, with Cavendish coming from behind and catching up with him, with both riders almost side-by-side as they approached the finish line of the 207.8km course.
But three-time winner Cavendish seemed to fade in the final moment, with Kittel able to just lunge enough to beat him by no more than half a wheel.
Greipel came across the line in third place, while Britain's Dan McClay (Fortuneo-Vital Concept) also snuck inside the top-10.
Unlike last year's edition, which saw a huge crash going into the final straight, there were no major incidents despite the strong wind and rain, after questions were raised about the safety of the Scheldeprijs course.
The day's main break got away relatively early on and managed to build a gap of around five minutes before things began to tumble Sander Helven (Topsport-Vlaanderen), Lieuwe Westra (Astana), Steven Tronet (Fortuneo-Vital Concept), Berden De Vries (Roompot), Nico Denz (Ag2r), Tomasz Kiendys (CCC) were all involved, and were left dangling at arms reach from the peloton until just under 60km to go.
A number of riders tried attacks on the way on towards the three finishing circuits, but none could make significant gains with Etixx working hard at the front for Kittel, bringing the race back for its traditional sprint finish.
While many of the big favourites for next Sunday's Paris-Roubaix took part in the mid-week classic, Tour of Flanders winner Peter Sagan (Tinkoff) and Ian Stannard (Sky) were among those who abandoned the race shortly before the finish as they looked to stay out of trouble.
Scheldeprijs 2016 (207.8km)
1. Marcel Kittel (Ger) Etixx-Quick-Step
2. Mark Cavendish (GBr) Dimension Data
3. André Greipel (Ger) Lotto-Soudal
4. Edward Theuns (Bel) Trek-Segafredo
5. Nicola Bonifazio (Ita) Trek-Segafredo
6. Danny van Poppel (Ned) Team Sky
7. Nikia Arndt (Ger) Giant-Alpecin
8. Wouter Wippert (Ned) Cannondale
9. Dylan Groenewegan (Ned) LottoNL-Jumbo
10. Daniel McClay (GBr) Fortuneo-Vital Concept, all same time
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