The coupling processes among the lithosphere, atmosphere, and ionosphere (LAI) during the earthquake preparation phase are still an open scientific debate. Comprehensive LAI coupling effects around the 2022 Ms6.8 Luding earthquake in China are investigated with a multi-parameter and multi-layer approach, including the b-value, revised accelerated moment release, Earth resistivity, ELF magnetic field emissions, atmospheric electric field, surface temperature, foF2 from ionosonde, GNSS TEC, Ne and magnetic field from CSES and Swarm satellites, and energetic electrons from CSES and NOAA satellites. It is found that the anomalies start from the lithospheric parameters as Earth resistivity and b-values 1–2 years before to reflect the local stress loading in the seismic region, then the ionospheric and atmospheric disturbances occur and accelerate −50 days before and −15 days before, and finally the electrons precipitate a few days before. The simultaneous perturbations in LAI illustrate the thermodynamic coupling channel, such as on 24 August, −12 days before. Meanwhile, the abundant developed ionospheric anomalies without atmospheric disturbances demonstrate the electromagnetic coupling way from the lithosphere to the ionosphere directly. Finally, the results demonstrate a two-way model of LAIC: one way is characterized by a slow chain of processes, of thermodynamic nature, starting from the ground and proceeding to the above atmosphere and ionosphere, showing an exponential trend in the cumulative number of anomalies; the second way is characterized by oscillating electromagnetic coupling between the lithosphere and ionosphere, showing intermittent fluctuations in the corresponding cumulative number of anomalies.