Stunting in developing countries continues to be a major public health problem. Measuring head circumference (HC) during clinical anthropometric assessment can help predict stunting. The aim of this study was to assess burden and determine the predictors of low HC (<- 2 SD) at birth and during first 2 years of life in a semi- urban settlement of Vellore. The study uses baseline data and serial HC measurements from the birth cohort of MAL-ED study, where 228 children from Vellore completed follow-up between March 2010 to February 2014. Analysis of baseline, maternal and paternal characteristics, micro-nutrient status and cognition with HC measurements was performed using STATA version 13.0 software. The mean HC (±SD) at 1st, 12th and 24th month were 33.37 (1.29) cm, 42.76 (1.23) cm and 44.9 (1.22) cm respectively. A third of the infants (75/228) had HC less than - 2 SD at first month of life, and on follow-up, 50% of the cohort had HC ≤ -2 SD both at 12th and 24th month. Low HC measurements at all three time-points were observed for 21.6% (46/222) infants. Low HC was significantly associated with stunting in 37.3% (OR = 10.8), 57.3% (OR = 3.1) and 44.4% (OR = 2.6) children at 1st, 12th and 24th month respectively. Bivariate analysis of low HC (<- 2 SD) at 12th month showed a statistically significant association with lower socioeconomic status, low paternal and maternal HC and low maternal IQ. Multivariable logistic regression analysis showed maternal (AOR = 0.759, 95% CI = 0.604 to 0.954) and paternal (AOR = 0.734, 95% CI = 0.581 to 0.930) HC to be significantly associated with HC attained by the infant at the end of 12 months. One-third of the children in our cohort had low head circumference (HC) at birth, with one-fifth recording low HC at all time-points until 2 years of age. Low HC was significantly associated with stunting. Paternal and maternal HC predicted HC in children. HC measurement, often less used, can be a simple tool that can be additionally used by clinicians as well as parents/caregivers to monitor child growth.