Oleksandr Pyshur opened the scoring on the stroke of half-time and Fozil Musaev sealed a surprise win for the Uzbek visitors four minutes from time.
In the other Group G encounter, South Korean side Pohang Steelers, the most successful team in Asia having won this competition on three occasions, were held to a goalless draw by Beijing Guoan.
Al Gharafa, with Tunisian Habib Sadek beginning his second spell as interim coach after the resignation at the weekend of Alain Perrin, opened their Group C campaign with a 2-0 defeat to Al-Ahly.
Mustafa Al-Bassas opened the scoring in the 35th minute for the Saudi Arabian side, who reached last year's final, and Victor Simoes scored a last-minute clincher.
Sepahan enjoyed a routine 3-0 win over Al Nasr.
Albanian striker Xhevahir Sukaj headed the Iranian champions ahead in the 22nd minute and made the game safe in the 81st when he turned home Mohammad Reza Khalatbari's cross from point-blank range after a well-worked short corner.
Omid Ebrahimi rounded off the scoring three minutes from time, turning home a Khalatbari cut-back that had eluded Sukaj, seeking a hat-trick.
Al Rayyan of Qatar fought back from a goal down on three occasions to claim a 3-3 draw against Esteghlal in Group D.
Goals from Jlloyd Samuel and Arash Borhani and Javad Nekounam's penalty put the Iran side in front on three occasions, but they were cancelled out by Rodrigo Tabata's spot-kick, Musa Haroon and former Brazil international Nilmar.
UAE Pro League champions Al-Ain edged past 10-man Saudi outfit Al Hilal, with former Sunderland striker Asamoah Gyan coming off the bench to seal a 3-1 victory in the final minute.
Abdulla Al-Zouri put Al-Hilal ahead in the ninth minute but Omar Abdulrahman struck just before the half-hour and Alex Brosque scored just after half-time, with the visitors' hopes of claiming a point hit by Salem Al-Dosari's 55th-minute dismissal before Gyan compounded their woes late on.
There was just one goal in the two Group G fixtures, with Cordova Cleo's strike on half-time enough to give Japanaese side Kashiwa Reysol a 1-0 win at Chinese Super League outfit Guizhou Renhe.
Central Coast Mariners of the A-League were held to a goalless draw by South Korea's Suwon Bluewings.
Wednesday's AFC Champions League Results
Sepahan 3-0 Al Nasr
Al Ahli 2-0 Al Gharafa
Al Ain 3-1 Al Hilal
Al Rayyan 3-3 Esteghlal
Sanfrecce Hiroshima 0-2 Bunyodkor
Pohang Steelers 0-0 Beijing Guoan
Central Coast Mariners 0-0 Suwon Samsung Bluewings
Guizhou Renhe 0-1 Kashiwa Reysol