Rice crops are especially vulnerable to arsenic exposure compared to other cereal crops because flooding growing conditions facilitates its uptake. Besides, there are still many unknown questions about arsenic’s mode of action in rice. Here, we apply two untargeted approaches using liquid chromatography coupled to mass spectrometry (LC-MS) to unravel the effects on rice lipidome and metabolome in the early stages of growth. The exposure is evaluated through two different treatments, watering with arsenic-contaminated water and soil containing arsenic. The combination of regions of interest (ROI) and multivariate curve resolution (MCR) strategies in the ROIMCR data analyses workflow is proposed and complemented with other multivariate analyses such as partial least square discriminant analysis (PLS-DA) for the identification of potential markers of arsenic exposure and toxicity effects. The results of this study showed that rice metabolome (and lipidome) in root tissues seemed to be more affected by the watering and soil treatment. In contrast, aerial tissues alterations were accentuated by the arsenic dose, rather than with the watering and soil treatment itself. Up to a hundred lipids and 40 metabolites were significantly altered due to arsenic exposure. Major metabolic alterations were found in glycerophospholipids, glycerolipids, and amino acid-related pathways.