In2261,theVorlonsjointheShadowWar,buttheirtacticsbecomeaconcernforthealliancewhentheVorlonsbegindestroyingentireplanetswhichtheydeemtohavebeen"influenced"bytheShadows.Disturbedbythisturnofevents,Babylon5recruitsseveralotherpowerfulandancientraces(theFirstOnes)totheircause,againstboththeShadowsandtheVorlons.CaptainJohnSheridanreturnstothestationafterescapingfromZ'ha'dum,butataprice:barringillnessorinjury,hehasonly20yearslefttolive.HeisaccompaniedbyamysteriousaliennamedLorienwhoclaimstobetheoldestsentientbeinginthegalaxy.
HoursbeforeSheridan'sreturn,Garibaldiisrescuedandreturnedtothestation,inratherdubiouscircumstances.HeismarkedlymoreparanoidandsuspiciousofotheralienracesandofSheridanthanhewasbefore.
CentauriEmperorCartagiaforgesarelationshipwiththeShadows.LondoMollariengineerstheassassinationofCartagiaandrepudiateshisagreementwiththeShadows.LondokillsMr.MordenanddestroystheShadowvesselsbasedontheCentaurihomeworld,inanattempttosavehisplanetfromdestructionbytheVorlons.Aidedbytheotherancientraces,andseveralyoungerones,SheridanluresboththeVorlonsandtheShadowsintoanimmensebattle,duringwhichtheVorlonsandShadowsrevealthattheyhavebeenleftasguardiansoftheyoungerraces,butduetophilosophicaldifferences,endedupusingthemaspawnsintheirendlesswarsthroughouttheages.Theyoungerracesrejecttheircontinuedinterference,andtheVorlonsandShadows,alongwiththeremainingFirstOnes,agreetodepartthegalaxyforever.
AftertheShadowsaredefeatedGaribaldileaveshispostassecuritychiefandworksonhisownasa"providerofinformation".HebeginsworkingforoneWilliamEdgars,aMarsTycoon,whoismarriedtoGaribaldi'sformerlove.WhileheworksevercloserwithEdgars,hebecomesincreasinglyaggressivetowardsSheridanandeventuallyleavesBabylon5.
MinbarisgrippedbyabriefcivilwarbetweentheWarriorandReligiouscastes.DelennsecretlymeetswithNeroonoftheWarriorcasteandconvinceshimthatneithersidecanbeallowedtowin.Shetellshimthatshewillundergoaritualwhereinshewillbewillingtosacrificeherself,butwillstoptheritualbeforesheactuallydies.WhenNeroonseesthatsheactuallyintendstogothroughtheentireritual,herescuesherandsacrificeshimselfinstead,declaringthat,althoughhewasbornWarrior,inhisheartheisReligious.
AspartoftheongoingconflictbetweenEarthandBabylon5,GaribaldieventuallybetraysSheridanandarrangeshiscaptureinordertogainEdgars'trustandlearnhisplans.GaribaldilaterlearnsthatEdgarscreatedavirusthatisdangeroustoonlytelepaths.Itisthenrevealed,thatGaribaldiwasactuallyabductedbythePsi-CorpsattheendofSeason3andre-programmedbyBestertoprovideinformationtohimattherighttime.BesterreleasesGaribaldiofhisprogramming,andallowshimtoremembereverythinghehasdonesincebeingkidnapped.Edgarsiskilledandhiswifedisappears,butisreunitedwithGaribaldiaftertheendofthewar.GaribaldihelpsfreeSheridanandreturnhimtothecampaigntofreeEarth.AnallianceledbyBabylon5freesEarthfromtotalitarianrulebyPresidentClarkinashortbutbloodywar.ThisculminatesinClark'ssuicideandtherestorationofdemocraticgovernment.Marsisgrantedfullindependence,andSheridanagreestoresignhiscommission.TheLeagueofNon-AlignedWorldsisdissolvedandreformedintotheInterstellarAlliance,withSheridanelectedasitsfirstPresidentandcontinuinghiscommandoftheRangers,whoaretoactasagalacticequivalentofUnitedNationspeacekeepers.
Intheseasonfinale,theeventsof100,500,1000,andonemillionyearsintothefutureareshown,depictingBabylon5'slastinginfluencethroughouthistory.Amongsttheeventsshownarethepoliticalaftermathofthe2261civilwar,asubsequentnuclearwaronEarthinvolvinganewtotalitariangovernmentintheyearAD2762,theresultingfallofEarthintoapre-industrialsociety,thelossandrestorationofhumanity'sknowledgeofspacetravel,andthefinalevolutionofmankindintoenergybeingssimilartotheVorlons,afterwhichEarth'ssungoesnova.
