This paper presents a monolithically integrated aptasensor composed of a piezoresistive microcantilever array and an on-chip signal processing circuit. Twelve microcantilevers, each of them embedded with a piezoresistor, form three sensors in a Wheatstone bridge configuration. The on-chip signal processing circuit consists of a multiplexer, a chopper instrumentation amplifier, a low-pass filter, a sigma-delta analog-to-digital converter, and a serial peripheral interface. Both the microcantilever array and the on-chip signal processing circuit were fabricated on the single-crystalline silicon device layer of a silicon-on-insulator (SOI) wafer with partially depleted (PD) CMOS technology followed by three micromachining processes. The integrated microcantilever sensor makes full use of the high gauge factor of single-crystalline silicon to achieve low parasitic, latch-up, and leakage current in the PD-SOI CMOS. A measured deflection sensitivity of 0.98 × 10−6nm−1and an output voltage fluctuation of less than 1 μV were obtained for the integrated microcantilever. A maximum gain of 134.97 and an input offset current of only 0.623 nA were acquired for the on-chip signal processing circuit. By functionalizing the measurement microcantilevers with a biotin-avidin system method, human IgG, abrin, and staphylococcus enterotoxin B (SEB) were detected at a limit of detection (LOD) of 48 pg/mL. Moreover, multichannel detection of the three integrated microcantilever aptasensors was also verified by detecting SEB. All these experimental results indicate that the design and process of monolithically integrated microcantilevers can meet the requirements of high-sensitivity detection of biomolecules.