Iranian state media blamed the al-Qaeda-linked Sunni extremist group Jaish al-Adl for the bombing.
There was no immediate claim of responsibility for the attack, which came on the day of a USA -led conference in Warsaw that included discussions on what America describes as Iran's malign influence across the wider Mideast.
A suicide auto bomb targeted a bus carrying members of the Guards, the Guards said in a statement on Wednesday. Images after the blast published by semi-official news agencies showed the explosion tore the bus apart, as passers-by used the light of their cellphones to illuminate the debris.
Meanwhile, the IRGC Qods Base has issued a statement, condemning the attack as a revenge for the failure of the foreign plots in the aftermath of the celebrations of the 40th anniversary of the 1979 Islamic Revolution.More news: Johnson Wins Season-Opening Clash at Daytona
The IRGC is a major economic and military power in Iran, answerable only to the country's supreme leader, Ayatollah Ali Khamenei. Some of its fighters are seasonal, including some from Pakistan, who are called upon for occasional operations against Iranian security forces.
Earlier this month, the group claimed responsibility for an attack on an IRGC base in southeastern Iran, killing one soldier and wounding five more.
Wednesday's attack was the deadliest in Iran since September, when gunmen killed at least 24 people at a military parade in the south-western city of Ahvaz. Thirteen people were wounded.
Local tribes control large swaths of Iran's Sistan and Baluchistan regions and neither Iranian nor Pakistani security forces have a permanent presence there.More news: DOJ: She Knew US Secrets and Gave Them to Iran
Iranian authorities blamed "jihadist separatists" for the assault claiming they were backed by Saudi Arabia, Israel and the United States. Trump withdrew the US from the accord last May.
Amid the new tensions, Iran's already-weakened economy has been further challenged.
Dubbing the meeting in Poland the "WarsawCircus", Iranian Foreign Minister Mohammad Javad Zarif said it was "no coincidence that Iran is hit by terror on the very day" that the talks began in the Polish capital. Zarif wrote on Twitter.More news: Asensio gives Madrid Real advantage