Pakistan has a high burden of hereditary and congenital anomalies and their incidence rate almost doubles against the background of parental consanguinity. Consanguineous unions (CU) are customary in Pakistan and deeply rooted socio-cultural norms favour CU. This study aimed to elucidate the determinants and temporal change in CU in four northwestern populations of Pakistan. In a cross-sectional study, data on marital union types, bio-demographic factors, and paternal consanguinity were collected from 6,323 ever-married individuals in four districts of northwest Pakistan: Haripur, Muzaffarabad, Mansehra, and Shangla. We used descriptive statistics and multivariable logistic regression analysis. The CU were calculated to be 55%, and inbreeding coefficient F (ICF) was estimated to be 0.029. Eight factors, including district, rural origin, age of husband, occupational group of husband, literacy of husband, parental consanguinity, exchange marriage, and extended family type, were found to be significant predictors of consanguinity in the multivariable logistic regression analysis. The rate of consanguinity decreased significantly in the younger age categories of individuals. The rate of CU was seen to be declining over time and in marriages that started ‘before 1980’ and ‘after 2010’, respectively, and there was a decline in ICF from 0.030 to 0.027. These analyses also showed that the literacy rate improved, the average age at marriage increased, and the frequency of exchange marriages decreased over time. This study employs a sizable first-hand dataset to demonstrate a lowering CU rate in northwest Pakistan. It is anticipated that the burden of inherited and congenital anomalies may likely to diminish in the study populations along with the fall in ICF.