An　innovative　ecosystem　services-based　sustainability　assessment　was　conducted　in　the　important　urban　agglomeration　of　the　Lake　Biwa　region,　Japan,　covering　the　time　period　from　1950　to　2014.　A　22-indicator　system　was　established　that　was　based　on　the　major　ecosystem　services　of　Lake　Biwa　and　its　water　courses,　i.e.,　provisioning　services　regarding　aquatic　products　and　water;　regulating　services　regarding　floods　and　water　quality;　cultural　services　regarding　recreation　and　tourism,　scientific　research,　and　environmental　education;　and　supporting　services　regarding　biodiversity.　First,　changes　in　the　eight　ecosystem　services　were　discussed　together　with　the　considerable　experience　and　difficult　lessons　that　can　be　drawn　from　the　development　trajectory.　Next,　with　the　indicators　rearranged　according　to　sustainability　principles,　the　regional　sustainability　over　the　past　six-plus　decades　was　assessed.　In　general,　this　urban　agglomeration　has　been　progressing　in　terms　of　its　sustainability,　although　economic　and　social　development　was　achieved　at　the　cost　of　environmental　degradation　in　the　past,　and　the　current　economic　downturn　is　hurting　the　balanced　development　and　integrated　benefits.　The　results　lead　directly　to　recommendations　for　regional　development,　especially　in　terms　of　economic　rejuvenation,　from　the　perspective　of　improving　management　of　Lake　Biwa＇s　water　resources.　Moreover,　the　relevant　knowledge　is　educational　and　inspirational　for　other　places　in　the　world　that　are　facing　similar　development　issues.　For　example,　the　effective　and　even　pioneering　countermeasures　that　have　been　taken　against　environmental　degradation,　as　well　as　the　participation　and　collaboration　of　multiple　stakeholders,　could　be　useful　as　a　model.　Moreover,　the　study　invites　increased　understanding　of　ecosystem　vulnerability　to　anthropogenic　devastation　and　emphasizes　the　priority　of　precautionary　measures　over　countermeasures　in　the　context　of　holistic　urban　planning　and　sustainable　urban　development.　©　2017　Elsevier　B.V.