The hosts took the lead in the 38th minute when good work by Komoliddin Tadjiev ended with Artur Geykorian firing a low finish under the body of keeper Seyed Rahmati.
Sepahan equalised in first-half stoppage time when an unmarked Ahmad Jamshidian headed home but substitute Geynrikh provided the vital intervention with his first touch as his 25-yard set-piece curled straight in after eluding everyone in a crowded penalty area.
The first effort on goal came from Sepahan's Moharram Navidkia as the midfielder tried his luck from 30 yards but was off target.
Keeper Temur Juraev's mistake then went unpunished by the Iranians before Pakhtakor had an opportunity in the 16th minute when Murod Khalmukhamedov's cross was taken on the chest by Milorad Janjus but the Serbian turned and shot over the bar.
Ilhom Suyunov fired a free-kick straight at Rahmati 10 minutes later before Sepahan created the most dangerous moment of the first-half thus far when Mahdi Karimian was given time and space to shoot in the box but Juraev comfortably saved his effort.
Pakhtakor took the lead in fine style in the 38th minute when Tadjiev picked the ball up just inside the opposition half and beat three men with a surging run before laying the ball off to Gevorkyan.
The midfielder's neat turn saw him cut back inside a defender and his low left-foot shot went under keeper Rahmati.
Sepahan then stunned the hosts with an equaliser in first-half stoppage time when a cross from the right drifted just over Khalmukhamedov's head and an unmarked Jamshidian headed into the far corner.
Darko Markovic directed a free header into the ground in the 54th minute and Bojan Miladinovic saw a fierce 30-yard free-kick bounce the wrong side of the post two minutes later although Rahmati may have had it covered.
The Sepahan keeper then did well to block Tadjiev's follow-up after Asqar Jadigerov's close-range header at the far post from Gevorkyan's cross hit the back of a defender.
Pakhtakor then took the lead in the 71st minute in slightly fortuitous circumstances.
Substitute Geynrikh had been on the field a matter of seconds before he chipped a free-kick in from the left that eluded everybody including a static Rahmati and bounced into the net.
Janjus failed to get a proper connection from seven yards after the ball had been knocked back into his feet but the hosts comfortably closed out their second victory of the group.