Experts said the findings should sway those who question whether the shot is worthwhile, since the flu can lead to deadly complications, particularly among the young and those with weakened immune systems.
The US Centers for Disease Control and Prevention recommends the flu vaccine for all people aged six months and over, but just under 37 percent of Americans received it last year.
According to the study, more than 5,200 children aged three to eight were assigned to receive either a Hepatitis A vaccine or a quadrivalent flu vaccine, designed to protect against four influenza strains.
Both vaccines were made by the British pharmaceutical giant GlaxoSmithKline, which funded the research.
The study was carried out at 15 sites in Bangladesh, the Dominican Republic, Honduras, Lebanon, Panama, the Philippines, Thailand and Turkey.
The flu shot was effective 59.3 percent of the time at preventing influenza A or B, observed via common flu symptoms and confirmed in laboratory tests.
And when researchers looked at how the flu shot worked at fending off harsher cases of sickness, such as pneumonia, brain swelling and seizures, they found an efficacy rate of 74.2 percent.
"Influenza vaccine has the potential to prevent death, even if it isn't as good at preventing mild disease," said Kenneth Bromberg, director of the Vaccine Research Center and chairman of pediatrics at The Brooklyn Hospital Center.
"Influenza vaccine should be looked at with that perspective. Vaccines that prevent death are of value," said Bromberg, who was not involved in the study.
Researchers found that the flu vaccine, when compared to the control shot, also was associated with "69 percent fewer medical visits, 75 percent fewer hospitalizations, 77 percent fewer absences from school and 61 percent fewer parental absences from work."
Gregory Poland, director of the Mayo Vaccine Research Group in Minnesota, described the research as "well-designed and conducted," and said it "confirms the contemporary value of influenza immunization in young children."
Until now, there had been no large research study that showed how well the quadrivalent flu vaccine worked at preventing illness in children.
"This study adds important information to our body of knowledge on prevention of childhood influenza," said Sunil Sood, chairman of pediatrics at Southside Hospital in Bay Shore, New York, who was not involved in the research.
It "bolsters the national recommendation to vaccinate every child six months and older every year against influenza."