Mohammad Nori put the visitors ahead after five minutes but the Uzbek side got back on level terms before half-time when skipper Odil Ahmedov converted a controversial penalty.
Stanislav Andreev then took advantage of poor defending to net the winner just after the interval to maintain Pakhtakor’s unbeaten record and keep them at the top of Group A with 10 points from four games.
The two-time semi-finalists will advance to the knockout stage for the first time since 2004 if Al Ahli of the United Arab Emirates fail to beat Al Hilal of Saudi Arabia later on Wednesday.
Saba needed a win to reignite their campaign after managing only two points from their first three games and made the perfect start at Pakhtakor Stadium.
Adel Kolahkaj swung in a dangerous free-kick from the left that goalkeeper Ignatiy Nesterov attempted to claw away from danger as it dipped beneath his crossbar.
However, he failed to get enough distance on his clearance and the ball was sent back into the middle where Nori was on hand to hook a shot in past a crowd of players.
After that early setback, Pakhtakor bossed possession and should have drawn level in the 25th minute when Alexander Geynrikh eluded the challenge of two defenders and put a dangerous ball into the box that was just out of the reach of a charging Farhod Tadjiyev.
Pakhtakor did not appear likely to get an equaliser at that stage but did so in the 35th minute after being awarded a fortuitous penalty when Tadjiyev went down under minimal contact from Morteza Kashi.
Goalkeeper Almir Tolja guessed right on the spot kick but could do little to keep out Ahmedov’s effort, which flew unerringly into the left corner.
The home side should have gone ahead in the 40th minute when Dilshod Sharofetdinov knocked down a cross for Geynrikh, who headed wide from inside the six-yard box.
The score remained tied at half-time but Pakhtakor took the lead just three minutes into the second half when Andreev capitalised on slack defending by the visitors.
Kashi should have cut off Geynrikh’s cross from the right but allowed the ball to bounce past him to an unmarked Andreev, whose volley bounced past reserve keeper Ershad Yousefi, on as a half-time substitute for Tolja, and just snuck in at the far post.
Saba’s best effort of an equaliser fell to Nori, whose dipping effort in the closing minutes was punched clear by Nesterov.
But Sadriddin Abdullaev should have put the game out of reach when his effort was cleared off the line by Morteza Asadi.