Abnormal fatty acid (FA) metabolism can change the inflammatory microenvironment and promote tumor progression and metastasis, however, the potential association between FA-related genes (FARGs) and lung adenocarcinoma (LUAD) is still unclear. In this study, we described the genetic and transcriptomic changes of FARGs in LUAD patients and identified two different FA subtypes, which were significantly correlated with overall survival and tumor microenvironment infiltrating cells in LUAD patients. In addition, the FA score was also constructed through the LASSO Cox to evaluate the FA dysfunction of each patient. Multivariate Cox analysis proved that the FA score was an independent predictor and created the FA score integrated nomogram, which offered a quantitative tool for clinical practice. The performance of the FA score has been substantiated in numerous datasets for its commendable accuracy in estimating overall survival in LUAD patients. The groups with high and low FA scores exhibited different mutation spectrums, copy number variations, enrichment pathways, and immune status. Noteworthy differences between the two groups in terms of immunophenoscore and Tumor Immune Dysfunction and Exclusion were observed, suggesting that the group with a low FA score was more responsive to immunotherapy, and similar results were also confirmed in the immunotherapy cohort. In addition, seven potential chemotherapeutic drugs related to FA score targeting were predicted. Ultimately, we ascertained that the attenuation of KRT6A expression impeded the proliferation, migration, and invasion of LUAD cell lines. In summary, this research offers novel biomarkers to facilitate prognostic forecasting and clinical supervision for individuals afflicted with LUAD.