Reactive coupling of functional polymer chains has been reported to be 3 orders of magnitude slower at static interfaces than under mixing conditions, and the reaction rates under mixing are close to the rates measured in homogeneous melts [Jeon et al. Prog. Polym. Sci. 2005, 30, 939]. However, due to the complexity of interfacial area generation during mixing, it was difficult to isolate the effects of flow on reaction kinetics. In this paper, a reactive multilayer system was created to explore this issue. A 640-layer polystyrene (PS)/poly(methyl methacrylate) (PMMA) sample was fabricated with a multilayer coextruder. Each component contained 10 wt % functional polymer, an amine-terminal PS (PS-NH2), and an anthracence-labeled anhydride-terminal PMMA (PMMA-anh-anth), respectively. Coupling reactions between PS-NH2/PMMA-anh-anth occurred during extrusion. The reaction conversion was measured with size exclusion chromatography, and interfacial morphology was monitored with both scanning and transmission electron microscopy. It was found that a significant amount of PS-b-PMMA copolymer formed during coextrusion, such that the interfaces of the extrudate were almost completely saturated with the block copolymers formed in situ. The coupling reaction of PS-NH2/PMMA-anh-anth under coextrusion was as rapid as that under mixing and was up to 1000 times faster than that under quiescent annealing. Subsequent steady shear of the multilayer samples further increased the reaction conversion significantly but destroyed the layer structure. Micelles and swollen micelles were formed under shear. Dynamic shear did not promote any further reaction due to the already high interfacial coverage for the extrudate. In contrast, for a simple laminated bilayer sample with nearly zero interfacial coverage, reactive coupling was promoted significantly by dynamic shear as evidenced by interfacial roughening. We speculate that the high surface energy of the functional chain ends causes them to be depleted near the interface, leading to very slow coupling under quiescent conditions. Moreover, the diffusion of polymer chains very close to the surface has been reported to be much slower than in bulk. Under coextrusion or mixing, external flow increased the functional group concentration in the interfaces, restoring reaction rates to the level expected under homogeneous conditions. The uniformity of block copolymer formation across the coextruded sample argues that extensional deformation is more important than shear in accelerating coupling.