The hosts, coached by Mohammad Mayelikohan, took an early lead through Karim Ansarifar after just 7 minutes in front of 15,000 spectators at Tehran's Azadi Stadium on Saturday.
The Reds then pushed forward in search of an equalizer but striker Mohsen Khalili failed to convert a penalty in the 40th minute of the game.
Saipa midfielder Mehdi Kheiri silenced the crowd when he doubled the advantage two minutes after the break.
"It was a fantastic game. We could have scored several goals in the first half but unfortunately we failed to use our opportunities well," Persepolis manager Ali Daei said.
"Our team also dominated the match in the second half, while Saipa didn't have any chances to score," he added.
The victory moved Saipa to the eight place in the IPL table with 38 points, while Persepolis stands third on 50.