Researchers measured the academic attainment of almost 6000 children against their body mass index.
The results showed that 466 girls classed as obese achieved poorer results aged 11, 13 and 16 years when compared to those of a healthy weight.
The link was less clear among boys, according to the team that led the study, from Dundee, Strathclyde and Bristol universities in collaboration with Georgia University in the US.
In English, maths and science, obese girls received results that were lower by an amount equivalent to a D instead of a C, which was the average in the sample.
Josie Booth, from Dundee University's school of psychology, said: "There is a clear pattern which shows that girls who are in the obese range are performing more poorly."
Around one-third of children aged between two and 15 are at risk of being overweight, including obese, according to figures from the Scottish Health Survey.
Professor John Reilly, the lead investigator from Strathclyde University, said: "It is clear that teenagers, parents and policy-makers in education and public health should be aware of the lifelong educational and economic impact of obesity."
The researchers said they took into account potentially distorting factors, such as poorer background, IQ and the age the girls began menstruating, but found they did not affect the overall results.
The study was funded by a Bupa Foundation grant to Strathclyde University.