Introduction: Despite treatment with antiemetic medications, nausea remains uncontrolled for many children receiving chemotherapy. One reason is that risk factors for nausea in children remain poorly explored. The purpose of this study was to identify risk factors for chemotherapy-induced nausea (CIN) in children. Methods: Prospective, observational study including 101 children (median age 6.4 years, range 0.8–17.9) with cancer receiving moderately or highly emetogenic chemotherapy. Primary endpoints were complete control of acute and delayed CIN, defined as no nausea in the acute phase 0–24 h after chemotherapy and in the delayed phase starting after the acute phase and ending 5 days later. Multivariable analyses included age, sex, cancer type, susceptibility to motion sickness, chemotherapy duration, numbers of antiemetics, co-administration with opioids or tricyclic antidepressants, and previously uncontrolled nausea or vomiting. Results: Acute CIN was associated with susceptibility to motion sickness (odds ratio [OR] 5.73, 95% confidence interval [CI] 1.36–33.7) and older age (OR 4.19, 95% CI 1.30–14.7), comparing age group 8–18 years with 0–3 years. Delayed CIN was associated with uncontrolled acute nausea or vomiting (OR 10.3, 95% CI 2.65–50.9), highly emetogenic chemotherapy (OR 8.26, 95% CI 1.17–76.8), and having a hematologic cancer type (OR 7.81, 95% CI 1.05–79.2). Conclusions: Susceptibility to motion sickness and age can influence the risk of acute CIN. More research is needed on how best to integrate risk information in preventive antiemetic strategies. Sufficient acute nausea and vomiting control are crucial to prevent delayed CIN.