Aiming at the complex relationship of water-energy-food (WEF) nexus and the lack of quantitative evaluation of system security, based on the analysis of the collaborative competition mechanism of WEF nexus, the system safety evaluation index system and evaluation method were constructed, and the quantitative evaluation was carried out by taking Xinjiang as examples. The results showed that the safety level value of WEF nexus in Xinjiang showed an increasing trend over time from 1997 to 2016. The trend of WEF nexus change in each prefecture presented two stages. Except for Karamay and Urumqi, the safety level values of WEF nexus were on the rise in other prefectures from 1997 to 2009, and the safety level values were significantly different. Half of the prefectures’ safety level values showed a downward trend, and the spatial difference of safety level values were decreased from 2010 to 2016. With the change of policy orientation and the continuous improvement of technology, carbon intensity was always an important factor affecting the WEF nexus safety of Xinjiang. And the other major factors were shifted from water and energy use in agriculture to renewable energy selfsufficiency and water security. Changes in influencing factors led to the obvious difference in the spatial pattern of the WEF nexus security between the two stages. The projection value ranking of each subsystem reflected the difference of driving mechanism among different prefectures. Some effective measures combined with the main influencing factors and regional characteristics could be taken to improve the WEF nexus safety.