Traditional calibration methods mostly focus on the calibration of detection systems while the calibration from the sampling and pre-condition systems to the detection system is usually ignored. In this regard, a Primary Standard Aerosol Mass Concentration Calibration System (PAMAS) is developed for the whole-process calibration of time-resolved aerosol measurement instruments. PAMAS is composed of a particle generation chamber, an ultrasonic atomizer, a dilution system, and a syringe pump. It is designed to steadily generate standard aerosol particles of known concentrations (≤250 μg/m3), chemical compositions, and stable particle size distributions. Monodispersed aerosol can be generated in the size range of hundreds of nanometers to several micrometers with a narrow size distribution. The generated particles with different compositions generated by PAMAS have been well verified by the filter-based gravimetric method, yielding accuracy and R2 of more than 95% and 0.999 in a wide concentration range. The response time by changing the target concentration of reference particles is 1–2 min. PAMAS has been applied to various types of time-resolved aerosol measurement instruments, including particle mass concentration monitors (Beta Attenuation and Tapered Element Oscillating Microbalance), online Ion Chromatograph, and semi-continuous OCEC carbon aerosol analyzer. Very consistent results between PAMAS and calibrated instruments can be obtained if the instruments are functioning well. As for instruments with certain technical issues, PAMAS can serve as a good tool for performance evaluation and quality assurance of the instruments and the accuracy of the measurement data can be adjusted based on the calibration results.