Aluminum (Al) toxicity is a major limitation to crop production in countries where acidic soil is abundant. In China, soybean production is constrained by Al stress-induced toxicity. As such, there is growing interest to develop Al-resistant varieties. In the present study, we sought to determine potential genes, functions and pathways for screening and breeding of Al-resistant varieties of soybean. First, we mined the E-GEOD-18517 dataset and identified 729 differentially expressed genes (DEGs) between untreated and Al-treated groups. Next, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathways enrichment analysis and observed that most of the screened genes were mainly enriched in defense response, plasma membrane and molecular transducer activity. They were also enriched in three important pathways, the phenylpropanoid biosynthesis, plant-pathogen interaction, and cutin, suberine and wax biosynthesis. Utilizing weighted gene co-expression network analysis of 815 DEGs screened by Venn diagram, we identified DEGs that were the most disparate between treated and untreated groups. LOC100793667 (probable protein phosphatase 2C 60, GLYMA_17G223800), LOC100780576 (ethylene-responsive transcription factor 1B, GLYMA_02G006200), and LOC100785578 (protein ESKIMO 1, GLYMA_02G258000) were the most differentially expressed, which were consistent with the qRT-PCR results. As these genes are known to participate in essential functions, such as cell junction and phenylpropanoid biosynthesis, these genes may be important for breeding Al-resistant varieties.