We　have　established　a　stable　regional　geodetic　reference　frame　using　long-history　(13.5　years　on　average)　observations　from　55　continuously　operated　Global　Navigation　Satellite　System　(GNSS)　stations　adjacent　to　the　Gulf　of　Mexico　(GOM).　The　regional　reference　frame,　designated　as　GOM20,　is　aligned　in　origin　and　scale　with　the　International　GNSS　Reference　Frame　2014　(IGS14).　The　primary　product　from　this　study　is　the　seven-parameters　for　transforming　the　Earth-Centered-Earth-Fixed　(ECEF)　Cartesian　coordinates　from　IGS14　to　GOM20.　The　frame　stability　of　GOM20　is　approximately　0.3　mm/year　in　the　horizontal　directions　and　0.5　mm/year　in　the　vertical　direction.　The　regional　reference　frame　can　be　confidently　used　for　the　time　window　from　the　1990s　to　2030　without　causing　positional　errors　larger　than　the　accuracy　of　24-h　static　GNSS　measurements.　Applications　of　GOM20　in　delineating　rapid　urban　subsidence,　coastal　subsidence　and　faulting,　and　sea-level　rise　are　demonstrated　in　this　article.　According　to　this　study,　subsidence　faster　than　2　cm/year　is　ongoing　in　several　major　cities　in　central　Mexico,　with　the　most　rapid　subsidence　reaching　to　27　cm/year　in　Mexico　City;　a　large　portion　of　the　Texas　and　Louisiana　coasts　are　subsiding　at　3　to　6.5　mm/year;　the　average　sea-level-rise　rate　(with　respect　to　GOM20)　along　the　Gulf　coast　is　2.6　mm/year　with　a　95%　confidence　interval　of　+/-　1　mm/year　during　the　past　five　decades.　GOM20　provides　a　consistent　platform　to　integrate　ground　deformational　observations　from　different　remote　sensing　techniques　(e.g.,　GPS,　InSAR,　LiDAR,　UAV-Photogrammetry)　and　ground　surveys　(e.g.,　tide　gauge,　leveling　surveying)　into　a　unified　geodetic　reference　frame　and　enables　multidisciplinary　and　cross-disciplinary　research.