The country has a moral duty to reopen schools next month, Boris Johnson said, as it emerged that there is "little evidence" of virus transmission in them.
Ensuring that all children return to school next month is now the "country's top priority", the prime minister said, because of the greater risk to them from the shutdown than coronavirus.
He stressed the urgency of getting all children in England back into class next month and after telling officials that schools will be the last to close if a nationwide lockdown is reimposed.
The coronavirus pandemic resulted in schools closing on March 20, ahead of many businesses. They will have been closed for more than five months by the start of the new academic year next month.
Mr Johnson is planning to visit a school on Monday to see first-hand how schools are preparing for all children to return and the "Covid-secure" measures they have in place.
The remarks came after unions suggested they could tell heads to keep schools shut if they did not consider them to be safe for teachers and students from the threat of coronavirus.
Last week Anne Longfield, the Children's Commissioner, told ministers that pubs and shops should be shut to reopen schools if a trade-off needs to be made because of a rise in coronavirus infections.
In meetings last week, according to Downing Street, the Prime Minister "stressed that the harm done to children’s education prospects by not attending school as well as to their mental health is far more damaging than the low risk posed" by the virus.
He told officials that there can be “no excuses” for children not returning to school this September and tasked ministers and government departments to continue working around the clock to ensure all children are able to smoothly return next month.
Ministers said the focus on getting children back to school suggests that No 10 is prioritising it ahead of getting office workers back to work.
A Downing St spokesman said: "The Prime Minister confirmed that children’s education must be the country’s top priority over the coming months and that in the event of a local lockdown, his expectation would be that schools would be the absolute last sector to be asked to close - and unprecedented steps would be taken to avoid this happening anywhere in the country.
"In the event of a more severe local lockdown where strong measures are needed in an entire town or city, the PM has been clear that businesses including shops, pubs and restaurants should be forced to close first, with schools remaining open for as long as possible."
The Government fears the recovery will stall unless people start going back to their workplaces in greater numbers but the comments will fuel the idea the focus now is on getting schools back before office workers.
A No 10 source said: “Teachers and schools across the country have made heroic efforts throughout this pandemic to keep schools open for those who have needed to attend and to provide excellent teaching online for those who have stayed at home, but nothing compares to the education children receive when they are physically at school.
“The Prime Minister has repeatedly stressed the importance of all children returning to school next month and recognises how hard schools across the country are preparing throughout the summer so that schools are safe to return to and all children can get the education they need.”