Compared to 1D structures, 2D structures have higher specific and active surface, which drastically improves electron transfer and extensibility along 2D plane. Herein, 2D-single crystal silver microflakes (AgMFs) are prepared for the first time in situ on reduced graphene oxide (RGO) by solvothermal synthesis with thickness around 100 nm and length around 10 μm. The oriented attachment mechanism is hypothesized to control the silver crystal growth and self-assembly of reduced silver units to form single-crystal AgMF structure on RGO sheets. Employing it as an electrode to fabricate reliable and extremely sensitive pressure sensors verifies the applicability of this novel 2D structure. Contrary to nanowires, 2D microflakes can intercalate better within the polymer matrix to provide an enhanced network for electron movement. The designed sensor can retain more than 4.7 MPa-1 after 10 000 cycles. The design proves functional for monitoring various actions such as wrist movement, squatting, walking, and delicate finger touch with high durability. A highly sensitive and flexible pressure sensor is fabricated based on the self-assembly of silver microflakes on reduced graphene oxide. This sensor exhibits an excellent pressure sensitivity as it can retain more than 4.7 MPa-1 after 10 000 cycles. This system is successfully used to monitor wrist movement, walking, and squatting and can be applied in touch screen panels, robotic systems, and prosthetics. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.