Dusan Savic had given Pakhtakor the lead after just three minutes but the home side fought back and soon levelled through Hawar Mohammed's deflected free-kick before Farhad Majidi's second goal of the tournament gave Esteghlal a half-time lead.
Substitute Mehdi Seyed Salehi's header early in the second period extended the lead and Esteghlal appeared to be cruising to three points before another replacement, Sanat Shikov, set-up a nervy finish with a late goal for Pakhtakor.
However, Arash Borhani finished off a powerful run with a clinical finish in stoppage time to make the points safe.
Both sides began the encounter locked together at the bottom of the table with just one point from their opening two games but it was Pakhtakor who made a dream start when Savic collected Stanislav Andreev's pass on the left flank, cut inside and fired a shot from 25 yards that took a healthy deflection off an Esteghlal defender and beat keeper Mohammad Mohammadi.
Opposite number Temur Juraev held Kianoush Rahmati's shot before Esteghlal levelled in the 11th minute when Mohammed's free-kick – awarded after Juraev had picked up a backpass - flicked off Khaki Makharadze's head in the wall and over the Pakhtakor keeper.
They took the lead 11 minutes later thanks to an error from Juraev. Iman Mobali's long ball from the right bounced beyond Igor Krimets and the defender and goalkeeper hesitated before the latter rushed out but missed the ball, giving Majidi the simple task of rolling it into the empty net.
Vladimir Kozak managed to find space in the Esteghlal box just before the half-hour mark but Mohammadi did well to block his effort before Majidi picked out Mohammed but his chip drifted just over the bar.
Esteghlal went further in front after 57 minutes when Salehi powered a header from Javad Shirzadeh's pinpoint cross past Juraev from six yards.
Mohammed then lashed a volley wide when unmarked in the box and Mohammadi had be alert to get down low at his near post to push Kozak's low shot around the post.
With time running out, Esteghlal wasted two good chances to wrap up the points. First, the Pakhtakor defence opened up to allow Borhani a good sight of goal but he shot wide before the striker's cut back picked out Salehi in space but he side-footed badly over from eight yards.
Pakhtakor reduced the arrears in the 90th minute when Shikov beautifully took down a long ball over the top before drilling a left-foot finish across Mohammadi and into the bottom corner.
It could have set up a nervous finish with four minutes of stoppage time still to play but Borhani put the result beyond doubt when he took advantage of a slip by a Pakhtakor defender to drive into the box before lifting a finish over Juraev.