Global dust storms (GDS) are an important dynamical phenomenon of the Martian lower atmosphere but are known to have important impacts on the Martian middle/upper atmosphere and ionosphere. Despite extensive studies over the past several decades, how the composition of the Martian ionosphere is modified during the GDS has only been studied from a theoretical point of view. Here we present for the first time the observations of the compositional variation of the Martian ionosphere during the GDS in 2018, using the ion density measurements made by the Neutral Gas and Ion Mass Spectrometer onboard the Mars Atmosphere and Volatile Evolution. At a representative altitude of 170 km, the variations of ionospheric species during the GDS show either enhancement (CO2+, Ar+, HO2+, H2O+, H2+, ArH+) or depletion (O2+, O+, N2+/CO+, OH+). Despite the apparent diversity, the observations are mostly understandable within the established framework of ionospheric chemistry on Mars, which further demonstrates that the variation of ion species during the GDS is a good diagnostic of the variation of relevant neutral species in the thermosphere. In particular, the observed ionospheric variation strongly supports a scenario that H2O is substantially enhanced in the Martian thermosphere during the GDS. However, the variations of O2+ and H2+ are inconsistent with predictions from ionospheric chemistry and require further investigation. Plain Language Summary Global dust storms (GDS) are an important dynamical phenomenon of the Martian climate that has been extensively studied over the past several decades. Though occurring in the lower atmosphere, they are known to have important impacts on the upper atmosphere and ionosphere, such as increasing the thermospheric water content, enhancing hydrogen escape, and lifting the ionospheric layer. Despite the existing efforts, how the composition of the Martian ionosphere is modified by has not been well studied. Owing to the accumulation of the ion density measurements made onboard the Mars Atmosphere and Volatile Evolution and the dust opacity measurements made onboard the Mars Reconnaissance Orbiter, we present for the first time a preliminary investigation of the species‐dependent variations of the dayside Martian ionosphere during the GDS in 2018. The responses of various ionospheric species to this event show diverse features, some demonstrating clear enhancement, whereas the others demonstrating clear depletion. Despite this, the observations are mostly consistent with the established ionospheric chemistry on Mars, implying that the variation of ionospheric species during a GDS is closely linked to the variation of neutral species in the thermosphere during the same event. Key Points Variations of the Martian ionosphere during global dust storms are species dependent, displaying either density enhancement or depletion The variations of most ion species except for O2+ and H2+ are interpreted using the ionospheric chemistry on Mars Substantial enhancement in thermospheric H2O on Mars during global dust storms are implied by ion measurements