Past studies of maternal smoking in pregnancy and ASD have been inconclusive, but the new Bristol University evidence changes that.
They assessed more than 14,500 participants of a long-term study into the effects of smoking in pregnancy for the study published in Scientific Reports.
By using information collected over many years, they were able to rule out other potential explanations for their results.
Lead author Professor Jean Golding said: "We already know that protecting a baby from tobacco smoke is one of the best things a woman can do to give her child a healthy start in life.
"Now we've found that not smoking during pregnancy could also give their future grandchildren a better start too."
She added that they have started studying the next generation of participants, which may show if the effect carries down another family layer.
Professor Marcus Pembrey, who was involved in the study, added: "In terms of mechanisms, there are two broad possibilities.
"There is DNA damage that is transmitted to the grandchildren or there is some adaptive response to the smoking that leaves the grandchild more vulnerable to ASD."
However, he said there was no explanation for the sex difference, and more research is needed to confirm the effects.
But he pointed to a study he previously worked on that found grand-maternal smoking is linked with different growth patterns in grandsons and granddaughters.
Smoking is known to damage the DNA of mitochondria - the numerous "power-packs" contained in every cell.
These are only transmitted to the next generation via the mother's egg.
Mutations often have no overt effect in the mother herself, but the impact can increase when transmitted to her own children, Professor Pembrey added.
It's estimated that about one in every 100 people in the UK has ASD. More boys are diagnosed with the condition than girls.
There's no "cure", but speech therapy and a number of other interventions are available to help children and parents.
Dangers of smoking while pregnant
Cigarettes can restrict the essential oxygen supply to the baby. As a result, their heart has to beat harder every time the mother smokes
Dangers include:
• Increased risk of complications in pregnancy and birth.
• Less likely to have a healthier pregnancy and a healthier baby.
• Increased risk of stillbirth.
• Baby more likely to be born too early and have to face the additional breathing, feeding and health problems that often go with being premature.
• Baby more likely to be born underweight: babies of women who smoke are, on average about 8oz lighter than other babies. This means they're more likely to struggle keeping warm and are more prone to infection.
• Increased risk of cot death
Each year, smoking during pregnancy in the UK causes an estimated:
• 2,200 premature births
• 5,000 miscarriages
• 300 stillbirths
Source: NHS