The blast ripped through a passenger bus on a main highway in Farah province, at around 6:00 am (0130 GMT), authorities said, killing mainly women and children.
"A passenger bus travelling on the Kandahar-Herat highway hit a Taliban roadside bomb killing 34 innocent people and wounding 17 others," said Muhibullah Muhib, a police spokesman for Farah province.
All were civilians, mostly women and children, he said.
Sediq Sediqqi, a spokesman for the Afghan presidency, confirmed the toll, blaming the incident on the Taliban.
Nasrat Rahim, the interior ministry spokesman, called the blast a "barbaric act of the terrorists".
There was no immediate confirmation from the insurgents that they were behind the blast.
The Taliban, which has resurged since its regime was toppled by the US invasion in 2001, made a vague pledge this month to reduce civilian casualties.
Civilians have long paid a disproportionate price in the nearly 18 years since the US invaded Afghanistan.
On Tuesday, the UN released a report showing that casualties have dropped 27 percent in the first half of 2019 compared to the same period last year, which was a record -- but nonetheless 1,366 civilians were killed and another 2,446 injured.
Child casualties represented almost a third of the overall total of civilian casualties.
The UN also said that US and pro-government forces caused more civilian deaths than the Taliban and other insurgent groups for the second quarter running.
It branded efforts to reduce the violence "insufficient".
The bloodshed is expected to intensify now that official campaigning for Afghanistan's presidential election, set for September 28, is underway.
At least 20 people were killed on Sunday, the first official day of the campaign, and 50 wounded when a suicide attacker and gunmen targeted the Kabul office of Afghan President Ashraf Ghani's running mate, Amrullah Saleh.
There are also doubts the election will happen at all, with lingering questions about whether Afghanistan should hold a key poll amid a months-long, US-led push to forge a peace deal with the Taliban.
This week US Secretary of State Mike Pompeo said that President Donald Trump wants to begin withdrawing troops before the vote, though he emphasised in comments to reporters Tuesday that there is "no deadline".
But the push has ignited widespread concern among Afghans that in Washington's rush to exit its longest war the Taliban will be returned to some semblance of power.