Although anxiety and depression are among the most prevalent mental disorders worldwide, they continue to gain less attention than their physical counterparts in terms of health care provision and population mentalisation. This cross-sectional study explores and compares the national prevalence of depression and anxiety signs/symptoms and well as identifying associated socio-demographic factors among Jordanian and Palestinian fertile couples. Four-hundred and sixty-nine participants were eligible for inclusion and agreed to participate in the study. The mean score for HAM-A and BDI-II were 12.3 ± 8.2 and 15.30 ± 10.0, respectively. According to the grading of HAM-A and BDI-II, the majority of the participants have graded themselves to be mildly anxious (N = 323, 68.9%) and around one third of participants (N = 148, 31.6%) moderately to severe depressed. The suicidal intent was remarkable and of concern where around 18.6% of participants had suicidal thoughts and wishes. There was a significant correlation between both HAM-score and BDI-II score and age [p = 0.01, p = 0.011, respectively], body weight [p = 0.01, p = 0.006, respectively], and total monthly income [p < 0.001, p < 0.001, respectively]. Our findings ought to alert healthcare professionals and other interested parties that there is a high burden of anxiety and depression symptoms among Jordanian and Palestinian couples. To support Jordanian and Palestinian couples’ mental health, healthcare professionals, researchers, and educators favoured to concentrate on creating efficient and culturally relevant education, preventive, and intervention procedures utilising evidence-based guidelines.