Ikon Daular Parthia a kan Mesopotamiya, wani yanki mai mahimmanci a tsohuwar Gabas ta Kusa, ya fara ne a tsakiyar karni na biyu KZ tare da Mithridates I na cin nasara na Parthia.Wannan lokacin ya nuna gagarumin sauyi a fagen siyasa da al'adu na Mesofotamiya, wanda ya sauya daga Hellenistic zuwa tasirin Parthia.Mithridates I, wanda ya yi mulki daga 171-138 KZ, an lasafta shi da fadada yankin Parthia zuwa Mesopotamiya.Ya kama Seleucia a shekara ta 141 K.Z., wani muhimmin lokaci da ke nuna raguwar ikon Seleucid da haɓakar ikon Parthia a yankin.Wannan nasara ba ta wuce nasarar soja ba;yana wakiltar ma'auni mai canzawa na iko daga Girkawa zuwa Parthians a Gabas Kusa.A ƙarƙashin mulkin Parthia, Mesopotamiya ya zama yanki mai mahimmanci don kasuwanci da musayar al'adu.Daular Parthia, wacce aka santa da juriya da bambancin al'adu, ta ba da damar addinai da al'adu daban-daban su bunkasa a cikin iyakokinta.Mesofotamiya, tare da tarihinta mai arziƙi da wurin dabarunta, ta taka rawar gani sosai a cikin wannan tukunyar narkewar al'adu.Mesopotamiya a ƙarƙashin mulkin Parthian ya ga hadewar abubuwan al'adun Girka da Farisa, waɗanda ke bayyana a cikin fasaha, gine-gine, da tsabar kuɗi.Wannan haɗin gwiwar al'adu ya kasance shaida ga ikon daular Parthia na haɗa tasirin tasiri daban-daban yayin kiyaye ainihinta.A farkon karni na 2 AD, Sarkin sarakuna Trajan na Roma ya jagoranci mamayewa zuwa Parthia, inda ya ci nasara a Mesofotamiya kuma ya mayar da ita lardin daular Romawa.Duk da haka, wannan iko na Romawa ya kasance ɗan gajeren lokaci, kamar yadda magajin Trajan, Hadrian, ya dawo Mesopotamiya zuwa Parthians ba da daɗewa ba.A wannan lokacin, Kiristanci ya fara yaɗuwa a Mesofotamiya, tun da ya isa yankin a ƙarni na 1 AZ.Roman Syria, musamman, ya fito a matsayin wani wuri mai mahimmanci ga addinin Kiristanci na Gabas da kuma al'adar adabin Siriya, wanda ke nuna gagarumin sauyi a yanayin addini na yankin.A halin yanzu, al'adun Sumerian-Akkadian na gargajiya sun fara dusashewa, wanda ke nuna ƙarshen zamani.Amfani da cuneiform, tsohon tsarin rubutu, shi ma ya ga raguwar sa.Duk da waɗannan sauye-sauyen al'adu, allahn Assuriyawa na ƙasar Ashur ya ci gaba da girmama shi a garinsa, tare da keɓe haikalinsa a ƙarshen ƙarni na 4 AD.^[45] Wannan yana nuna ci gaba da girmamawa ga wasu sassa na tsoffin al'adun addini na yankin a cikin haɓaka sabbin tsarin imani.