The Guard, which answers only to Iran's Supreme Leader Ayatollah Ali Khamenei, issued a statement saying a vehicle loaded with explosives targeted a bus carrying border guards affiliated with its force.
"The suicide attack on an Islamic Revolutionary Guards Corps personnel bus happened on the Khash-Zahedan road", IRNA said.
No group immediately claimed responsibility for the attack. The Revolutionary Guard later reported on its website that 27 were killed and 13 wounded.
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The statement did not identify the "hegemonic powers", but Iran's foreign minister linked the bombing to a US-led conference on the Middle East taking place in Warsaw, Poland, that will include discussions about Iran's activities in the region.
While violence and bomb attacks are not uncommon on both Iran's western and eastern frontiers - bordering Iraq and Afghanistan respectively - audacious and organised assaults that directly target the Islamic Republic's security services are still rare.
Jaish al-Adl emerged as the main armed opposition movement in the southeast after members of another Sunni group, Jundullah, joined it after their leader was captured on a plane in 2010. In December, another deadly suicide bombing targeted police in the city of Chabahar.
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Iran's Shi'ite Muslim authorities say militant groups operate from safe havens in Pakistan and have repeatedly called on the neighboring country to crack down on them.
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.
"Is it no coincidence that Iran is hit by terror on the very day that (hashtag) WarsawCircus begins?" "USA seems to always make the same wrong choices, but expect different results", Iranian foreign minister Javad Zarif said in reaction to the attack.
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The group, which is based in Pakistan, opposes the government in Tehran and has in the past carried out successful attacks against Iranian troops, including kidnappings, and an April 2017 ambush on the Pakistan border that killed nine border guards.