Four Tornados took off from RAF Akrotiri in Cyprus shortly after MPs voted to approve bombing.
The strikes targeted the Omar oil fields in eastern Syria, which is under IS control, and were "successful", Defence Secretary Michael Fallon said.
He had personally approved the targets ahead of the Commons vote, he said.
On Wednesday, MPs voted by 397 votes to 223 for UK military action against IS - also known as Daesh - in Syria after a 10-hour Commons debate.
The first Typhoon jet fighters have left RAF Lossiemouth in Moray, Scotland, to join the air strikes.
Mr Fallon said the Ministry of Defence would be assessing the damage done by the bombing later, but the aim was to strike "a very real blow on the oil and revenue on which Daesh depends".