Researchers measured the academic attainment of almost 6,000 children against their body mass index (BMI).
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, said to be the most comprehensive of its kind.
The research was conducted by 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 than their counterparts in the healthy weight range throughout their teenage years."
Professor John Reilly, the lead investigator from Strathclyde University, said: "Further work is needed to understand why obesity is negatively related to academic attainment, but 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 published in the International Journal Of Obesity was funded by a Bupa Foundation grant to Strathclyde University.