An increasing amount of waste seashells in China has caused serious environmental pollution and resource waste. This paper aims to solve these problems by using waste seashells as modified materials to prepare high-performance modified asphalt. In this study, seashell powder (SP) and stratum corneum-exfoliated seashell powder (SCESP) were adopted to prepare 10%, 20% and 30% of seashell powder-modified asphalt (SPMA) and stratum corneum-exfoliated seashell powder-modified asphalt (SCESPMA) by the high-speed shear apparatus, respectively. The appearance and composition of two kinds of SPs were observed and determined by the scanning electron microscope (SEM). The types of functional groups, temperature frequency characteristics, low temperature performance and adhesion of SPMA were tested by the Fourier-transform infrared (FTIR) spectrometer, dynamic shear rheometer (DSR), bending beam rheometer (BBR) and contact angle meter. The results show that the SP and SCESP are rough and porous, and their main component is CaCO3, which is physically miscible to asphalt. When the loading frequency ranges from 0.1 Hz to 10 Hz, the complex shear modulus (G*) and phase angle (δ) of SPMA and SCESPMA increase and decrease, respectively. At the same load frequency, SCESPMA has a larger G* and a smaller δ than SPMA. At the same temperature, SCESPMA has a larger rutting factor (G*/sin δ) and better high-temperature deformation resistance than SPMA. SP and SCESP reduce the low-temperature cracking resistance of asphalt, of which SCESP has a more adverse effect on the low-temperature performance of asphalt than SP. When SP and SCESP are mixed with asphalt, the cohesion work (Waa), adhesion work (Was) and comprehensive evaluation parameters of water stability (ER1, ER2 and ER3) of asphalt are improved. It is shown that both SP and SCESP have good water damage resistance, of which SCESP has better water damage resistance than SP. These research results have important reference value for the application of waste biological materials in asphalt pavement.