The German sprinter beat Zdenek Stybar and Jerome Pineau to the line on wet cobbles after fighting through the Omega Pharma-Quick Step lead out.
Frenchman Pineau held on for third after leading out Czech Stybar at the conclusion to the 180.2km stage from Berck-sur-Mer.
Argos-Shimano led the peloton for much of the wet stage while there was a long breakaway from Rony Martias (Saur-Sojasun), Carlos Quintero (Colombia-Coldeportes), Fabien Bacquet (Auber 93) and Franck Vermeulen (Véranda Rideau-Super U).
They were 4:35 clear with 70km to go but were reeled in on the two 25.9km circuits which ended the stage - Quintero and Vermeulen staying ahead longest - with Omega Pharma-Quick Step leading the attack.
Dmitriy Gruzdev (Astana) had a lone attack late on before Omega Pharma-Quick Step began their push for the line with a kilometre to go - and Degenkolb plotted his perfect assault to win.
1. John Degenkolb (Ger) Argos-Shimano
2. Zdenek Stybar (Cze) Omega Pharma-Quick Step
3. Jérôme Pineau (Fra) Omega Pharma-Quick Step
4. Nacer Bouhanni (Fra) FDJ-BigMat
5. Lloyd Mondory (Fra) AG2R La Mondiale
6. Danilo Napolitano (Ita) Acqua & Sapone
7. Kevin Ista (Bel) Accent.jobs-Willems Verandas
8. Egidijus Joudvalkis (Ltu) Landbouwkrediet-Euphony
9. Kenny van Hummel (Ned) Vacansoleil-DCM
10. Sébastien Hinault (Fra) AG2R La Mondiale