Four mountain rescue teams were called to separate incidents at the summits of Corn Du and Cribyn.
One person is being treated at Swansea's Morriston Hospital for burns. The other is at Prince Charles Hospital in Merthyr Tydfil.
Some rescuers were training in the area when the incidents happened.
An RAF Sea King from Chivenor was sent to aid two casualties on Cribyn and road ambulances and police were also sent to the scene.
Brecon Mountain Rescue Team were ending their exercise due to the electric storm when they received a call-out.
Its team doctor reached the first male casualty on Corn Ddu within 35 minutes.
Spokesman Mark Jones said passing cadets who had been on the summit at the time of the strike had already started resuscitation when the rescue doctor took over.
"I've been in Brecon Mountain Rescue for 30 years and I've never known anything like this," he said.
"It is exceptionally unusual, and for multiple people to be hit in multiple strikes on different peaks - it is very, very rare."
Three other mountain rescue teams - Central Beacons, Longtown and Western Beacons - were also called out.
A Dyfed-Powys Police spokesperson said: "As a result of these incidents, two men have sadly died, one man is in a serious condition in hospital and another man is in hospital but did not sustain serious injuries.
"Officers have informed the next of kin of the deceased men."
Two men are being treated in hospital after lightning strikes in the Brecon Beacons which killed two other men on Sunday.