In clinical drug development, two fundamental questions remain unanswered: what is the success rate of drugs in clinical trial? how does such rate change over time? Herein, a systematic analysis on the dynamic change of drugs’ clinical success rates (ClinSRs) using data from 20,398 clinical trial pipelines of 9,682 unique molecular entities during the past two decades was presented. Our analysis discovered that ClinSRs had been declining since the beginning of 21st century, and hit the bottom in recent years even substantially lower than previous estimates. In-depth assessments further reported great variation among the ClinSRs of various diseases, developmental strategies, and drug modalities. A platform ‘ClinSR.org’ (http://ClinSR.idrblab.org/) was finally constructed online to enable the illustration of how ClinSR dynamically changes over time, automated update of ClinSR for the coming decade, and customized calculation of ClinSRs for any drug group of interest. In sum, this study met the critical demand for accurate, timely and persistent assessment of ClinSR, for now and the future, to aid pharmaceutical and economic decision making.