This study investigated changes in the extraction characteristics of Jerusalem artichoke (Helianthus tuberosus L.) tubers (JA) using high hydrostatic pressure (HHP) treatment alone and in combination with enzymes and/or fermentation. HHP treatment of JA increased the soluble solid content and decreased the turbidity compared to the control group that received hot-water extraction. This indicates improved extractability of JA by HHP treatment alone or in combination. Combined HHP treatment with enzymes increased the contents of non-reducing sugars, fructooligosaccharide (FOS), and free amino acids in the extracts compared to those of control, thus activating browning reaction. Extraction of fermented JA by HHP treatment with or without enzyme showed increased polyphenol content as well as improved 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and superoxide dismutase (SOD) like activity compared to the control group. Taken together, HHP treatment of fermented JA with enzymes significantly improved the extractability of bioactive molecules such as phenolics and FOS compared to conventional water extraction or HHP treatment alone. Our results provide useful information for the improvement of raw material extraction by HHP treatment in combination.