UK experts studied brain scans of 120 men and women, with half of those studied having autism.
The differences found in the research, published in journal Brain, show more work is needed to understand how autism affects girls, the scientists say.
Experts said girls with the condition could be more stigmatised than boys – and it could be harder for them to be diagnosed at all.
Autism affects 1% of the population and is more prevalent in boys, so most research has focused on them.
In this study, scientists from the Autism Research Centre at the University of Cambridge used magnetic resonance imaging (MRI) to examine how autism affects the brain of males and females.
Male and female brains differ anyway – tissue volume is greater in males.
The study looked at the difference between the brains of typical males and those with autism – and then females with and without autism.
They found the brains of females with autism “look” more like – but still not the same as – healthy males, when compared with healthy females.
But the same kind of difference was not seen in males with autism – so their brains did not show “extreme” male characteristics.
Dr Meng-Chuan Lai, who worked on the study said: “What we have known about autism to date is mainly male-biased.
“This research shows that it is possible that the effect of autism manifests differently according to one’s gender.
“Therefore we should not blindly assume that everything found for males or from male-predominant mixed samples will apply to females.”
He said future research may need to look at males and females equally to discover both similarities and differences.
Dr Lai added: “Lastly, there really needs to be more research and clinical attention toward females ‘on the spectrum’.”
Carol Povey, Director of The National Autistic Society’s Centre for Autism, said: “Historically, research on autism has been largely informed by the experiences of men and boys with the condition.
“This important study will therefore help our understanding of how the condition differs between genders.”
She added: “Girls can be more adaptive than boys and can develop strategies that often mask what we traditionally think of as the signs of autism.
“This “masking” can lead to a great deal of stress, and many girls go on to develop secondary problems such as anxiety, eating disorders or depression.
“It’s important that we build on this study and more research is conducted into the way autism manifests in girls and women, so that we can ensure that gender does not remain a barrier to diagnosis and getting the right support.”