Organisers expect more than one million young people will participate in at least 110 countries on Friday.
The protesters are calling for politicians and businesses to take action to fight climate change.
The strikes are inspired by school student Greta Thunberg who protested outside Sweden's parliament in 2018.
Carrying a "school strike for climate change" sign, the then 15-year old said she was refusing to attend classes until Swedish politicians took action.
Her example inspired various movements across Europe, the US and Australia, known as Fridays For Future or School Strike for Climate.
The last co-ordinated international protest took place on 15 March, with an estimated 1.6 million students from 125 countries walking out of school.
This Friday's protests started in Australia and New Zealand, and are expected to be picked up across Asia, Europe, Africa and the Americas.
"I'm worried about all the weather disasters," Nina Pasqualini, a 13-year-old at a rally in Melbourne, told the Reuters news agency.
"Every time we have huge a bushfire here another animal might go extinct."
Australia just had its hottest summer on record and climate change is seen as the cause of the increasing frequency and severity of droughts, heat waves, floods and the melting of glaciers around the world.
In 2018, global carbon emissions hit a record high and UN-backed panel on climate change last October warned that to stabilise the climate, emissions will have to be slashed over the next 12 years.
Earlier this month, a UN report warned that one million animal and plant species were now threatened with extinction.