Stable isotopes in precipitation and vapor are a powerful tool for tracing the origin of moisture and mixing processes. This paper discusses time and space variation of δ18O in precipitation and controlling features over upper Blue Nile Basin using data from GNIP, observed data in 2014 and simulated data by AGCM. IsoGSM simulation in precipitation was verified with observation. The δ18O variation shows clear seasonality with the lowest 18O values in August and dry season, and enriched 18O in spring, June and September. Spring sample is enriched compared to summer, and assumed to be related with moisture sources. More enriched isotopes in spring and lower d-excess could be related to the source of air masses in short travel path from North Indian Ocean, Mediterranean and Red sea while summer rain is depleted with larger d-excess could be related to longer travel path of moisture from south Indian Ocean with mixing of potential evaporated moisture from open surface and transpired moisture from Congo vegetation and also from Gulf of Guinea. The isotopic statistics of three stations shows maximum, minimum and average value of (8.23‰, -11.73‰, 0.04‰) in Addis Ababa, (5.26‰, -12.74‰, and -2.52‰) in Entoto Hill and (4.08‰, -9.65‰, 2.41‰) in Debremarkos respectively. The δ2H- δ18O relationships, monthly weighted d-excess variation in the Basin revealed the temporal variation of δ18O in precipitation is essentially shaped by the source of the moisture and spatial differences is due to Rayleigh rainout effect along the moisture trajectory. The source of moisture is primarily controlled by the north south movement of ITCZ within the Basin. The study recommends the use of model simulated δ18O as good alternative for hydrological and hydrologeological investigations when needed.