Children are at increased risk of influenza-related complications. Public health agencies recommend 2 doses of influenza vaccine for children 6 months through 8 years of age receiving the vaccine for the first time. To systematically review studies comparing vaccine effectiveness (VE) and immunogenicity after 1 or 2 doses of inactivated influenza vaccine (IIV) in children. Data sources included Medline, Embase, and Cochrane Library databases. We included studies published in a peer reviewed journal up to April 2, 2019, with available abstracts, written in English, and with children aged 6 months through 8 years. VE among fully and partially vaccinated children was compared with that of unvaccinated children. We extracted geometric mean titers of serum hemagglutination inhibition (HAI) antibodies against influenza A(H1N1), A(H3N2), and B-lineage vaccine antigens after 1 and 2 IIV doses. Outcomes were evaluated by age, timing of doses, vaccine composition, and prevaccination titers. A total of 10 VE and 16 immunogenicity studies were included. VE was higher for fully vaccinated groups than partially vaccinated groups, especially for children aged 6-23 months. Our findings show increased HAI titers after 2 doses, compared with 1. Older children and groups with prevaccination antibodies have robust HAI titers after 1 dose. Similar vaccine strains across doses, not the timing of doses, positively affects immune response. Few studies focused on older children. Researchers typically administered one-half the standard dose of IIV. HAI antibodies are an imperfect correlate of protection. Findings support policies recommending 2 IIV doses in children to provide optimal protection against influenza.