It　remains　a　daunting　task　to　quantify　the　configurational　entropy　of　a　material　from　atom-revolved　electron　microscopy　images　and　correlate　the　results　with　the　material＇s　lattice　thermal　conductivity,　which　strides　across　statics,　dynamics,　and　thermal　transport　of　crystal　lattice　over　orders　of　magnitudes　in　length　and　time.　Here,　a　proof-of-principle　study　of　atomic-scale　visualization　and　quantification　of　configurational　entropy　in　relation　to　thermal　conductivity　in　single　crystalline　trigonal　GeSb2Te4　(aka　t-GeSb2Te4)　with　native　atomic　site　disorder　is　reported.　A　concerted　effort　of　large　t-GeSb2Te4　single　crystal　growth,　in-lab　developed　analysis　procedure　of　atomic　column　intensity,　the　visualization　and　quantification　of　configurational　entropy　including　corresponding　modulation,　and　thermal　transport　measurements　enable　an　entropic　＂bottom-up＂　perspective　to　the　lattice　thermal　conductivity　of　t-GeSb2Te4.　It　is　uncovered　that　the　configurational　entropy　increases　phonon　scattering　and　reduces　phonon　mean　free　path　as　well　as　promotes　anharmonicity,　thereby　giving　rise　to　low　lattice　thermal　conductivity　and　promising　thermoelectric　performance.　The　current　study　sheds　lights　on　an　atomic　scale　bottom-up　configurational　entropy　design　in　diverse　regimes　of　structural　and　functional　materials　research　and　applications.