Abstract: This study presents signatures of seismo-ionospheric perturbations possibly related to the 14 July 2019 M_w 7.2 Laiwui earthquake, detected by a cross-validation analysis of total electron content (TEC) data of the global ionospheric map (GIM) from GPS and plasma parameter data recorded by the China Seismo-Electromagnetic Satellite (CSES). After separating pre-seismic ionospheric phenomena from the ionospheric disturbances due to the magnetospheric and solar activities, we have identified three positive temporal anomalies, around the epicenter, at 1 day, 3 days and 8 days before the earthquake (14 July 2019), along with a negative anomaly 6 days after the earthquake. These results agree well with the TEC spatial variations in latitude–longitude–time (LLT) maps. To confirm these anomalies further, we employed the moving mean method (MMM) to analyze ionospheric plasma parameters (electron, \mathrmO^+ and \mathrmH\mathrme^+ densities) recorded by the Langmuir probe (LAP) and Plasma Analyzer Package (PAP) onboard the CSES. The analysis detected on, on Day Two, Day Four, and Day Seven before the earthquake, remarkable enhancements along the orbits around when in proximity to the epicenter. To make the investigations still more convincing, we compared the orbits on which anomalous readings were recorded to their corresponding four nearest revisiting orbits; the comparison did indeed indicate the existence of plasma parameter anomalies that appear to be associated with the Laiwui earthquake. All these results illustrate that the unusual ionospheric perturbations detected through GPS and CSES data are possibly associated with the M_w7.2 Laiwui earthquake, which suggests that at least some earthquakes may be predicted by alertness to pre-seismic ionospheric anomalies over regions known to be at seismic risk. This case study also contributes additional information of value to our understanding of lithosphere–atmosphere–ionosphere coupling.