Background Maternal psychological factors like depression, anxiety and stress have been associated with infant fussiness or colic. However, little research exists on whether positive factors such as social support and the happiness of the mother–partner relationship are associated with lower rates of infant fussiness or colic. Objectives We investigated the association between infant colic and three types of maternal support: general maternal social support (during pregnancy and post partum), the happiness of the mother–partner relationship (during pregnancy and post partum) and partner involvement in caring for the newborn. Methods Participants were 3006 women in the First Baby Study, a prospective study of the effect of mode of first delivery on subsequent childbearing. Women were interviewed by telephone during pregnancy and 1 month after first childbirth and asked about social support and if their baby had a variety of problems since birth, including ‘Colic – crying or fussiness three or more hours a day’. Multivariable logistic regression models were used to model the association between maternal support and infant colic, controlling for confounders, including maternal race or ethnicity, insurance, marital status, smoking, mode of delivery, maternal post‐partum depression, breastfeeding, other neonatal illnesses and newborn gestational age. Results Infant colic was reported by 11.6% of new mothers. High general maternal social support (in comparison with low), measured during pregnancy, was associated with lower reported infant colic (adjusted odds ratio (AOR), 0.55, 95% confidence interval (CI), 0.40–0.75) and measured post partum (AOR, 0.51, 95% CI, 0.39–0.67); high relationship happiness (in comparison with low), measured during pregnancy (AOR, 0.71, 95% CI, 0.54–0.93), and measured post partum (AOR, 0.22, 95% CI, 0.12–0.40); and high partner involvement with newborn care (in comparison with low) (AOR, 0.60, 95% CI, 0.44–0.81). Conclusion Higher levels of maternal social support during pregnancy and post partum are associated with lower rates of maternal reported infant colic.