The prediction of natural disasters in general and earthquakes, in particular, is becoming increasingly critical in providing early warnings and mitigating catastrophes’ effects. This study investigates relations between earthquakes and ionospheric disturbances. Based on analyzing TEC disturbances, we search for the impact of the earthquake-related seismic waves on the ionosphere. The study is designed as cross-sectional investigations, in which the global earthquakes are randomly collected by the cluster sampling method. We use data of 54 permanent GNSS (Global Navigation Satellite Systems) stations and global earthquakes with magnitudes (Mw) from 4.0 to 9.0 in the period from 2006 to March 2020. The selected data ensure strict conditions such as accuracy, the distance from the GNSS stations to the epicenter, and the depth of hypocenter. Probability and statistics are applied to filter, classify and analyze data. The results indicate that TEC fluctuations at the regions occurring earthquakes with magnitudes greater than 6.0 Mw are significant. These TEC anomalies appear from 30 minutes to around two hours before the mainshocks, and the oscillations remain from five to eight minutes. These TEC variations occur from five to eleven days before the great earthquakes. The results reveal the relations between ionospheric anomalies and earthquake-related seismic waves. The findings are the base to filter TEC anomalies generated by earthquakes in building ionospheric models. The study also opens up a prospect for GNSS applications in studying TEC anomalies linked to earthquake precursors as well.