Heterogeneity of carcinoma-associated fibroblasts (CAF) has long been recognized, but the functional significance remains poorly understood. Here we report the distinction of two CAF subtypes in oral squamous cell carcinoma (OSCC) that have differential tumor-promoting capability, one with a transcriptome and secretome closer to normal fibroblasts (CAF-N) and the other with a more divergent expression pattern (CAF-D). Both subtypes supported higher tumor incidence in NOD/SCID Ilγ2(null) mice and deeper invasion of malignant keratinocytes than normal or dysplasia-associated fibroblasts, but CAF-N was more efficient than CAF-D in enhancing tumor incidence. CAF-N included more intrinsically motile fibroblasts maintained by high autocrine production of hyaluronan (HA). Inhibiting CAF-N migration by blocking HA synthesis or chain elongation impaired invasion of adjacent OSCC cells, pinpointing fibroblast motility as an essential mechanism in this process. In contrast, CAF-D harbored fewer motile fibroblasts, but synthesized higher TGF-β1 levels. TGF-β1 did not stimulate CAF-D migration, but enhanced invasion and expression of epithelial-mesenchymal transition (EMT) markers in malignant keratinocytes. Inhibiting TGF-β1 in 3D cultures containing CAF-D impaired keratinocyte invasion, suggesting TGF-β1-induced-EMT mediates CAF-D-induced carcinoma cell invasion. TGF-β1-pretreated normal fibroblasts also induced invasive properties in transformed oral keratinocytes, indicating that TGF-β1-synthesizing fibroblasts, as well as HA-synthesizing fibroblasts, are critical for carcinoma invasion. Taken together, these results discern two subtypes of CAF that promote OSCC cell invasion via different mechanisms.