Cusco Sisixeko esilikomkhulu sesebe esinegama elifanayo ebekwe kumazantsi mpuma elizwe, kubandakanya iindawo zeentaba kunye nehlathi. Igama livela kwiQuechua Qusqu okanye eQosqo oko kuthetha ukuba liziko, inkaba, ibhanti; Kungenxa yokuba, ngokweentsomi zeInca, imihlaba engezantsi, ebonakalayo kunye nephakamileyo yahlangana kuyo. Ukusukela ngoko, isixeko sabizwa ngokuba sisenkaba sehlabathi.
Xa aboyisi baseSpain bafika, igama labo labizwa ngokuba yiCastilianized to Cuzco okanye Cusco. Omabini la magama asetyenziswa de kwangowe-1993, xa igama leCusco lenziwa laba semthethweni, nangona kumazwe athetha iSpanish abizwa ngokuba yiCuzco. Ngomhla kaNovemba 15, 1533, idolophu yaseCuzco yasekwa nguFrancisco Pizarro, emisela iPlaza de Armas kwindawo egcinwayo kude kube ngoku kwaye yayikwisikwere esiphambili ngexesha loBukhosi beInca. UPizarro wanika uCuzco igama leCiudad Noble y Grande, ngoMatshi 23, 1534.
NgoDisemba 9, 1983 eParis, I-UNESCO ibhengeza isixeko saseCusco njengeLifa leMveli leNkcubeko, iyenza eyona ndawo yokhenketho ibaluleke kakhulu ePeru. Umbindi wedolophu ugcina izakhiwo, izikwere kunye nezitalato ukusuka kumaxesha angaphambi kweSpanishi kunye nolwakhiwo lwamakholoniyali. Phakathi kwezinto ezinomtsalane esixekweni zezi: Indawo yaseSan Blas apho amagcisa kunye neevenkile zawo zobugcisa zigxile, zenza ukuba ibe yenye yezona ndawo zintle esixekweni; Isitrato iHatun Rumiyoq esikhokelela kwiBarrio de San Blas kwaye apho ungabona khona ilitye elidumileyo leengile ezilishumi elinambini.
Okumangalisa ngokulinganayo yiConvent kunye neCawe yaseLa Merced apho izitena zohlobo lweRenaissance Baroque zivelile, kunye nezitali zeekwayala, imizobo yobukoloniyali kunye nemizobo yeenkuni; Kukwakho neCathedral, iPlaza de Armas, iCawe yeNkampani, iQoricancha kunye neSanto Domingo Convent.