The Buccaneers advanced 3-2 on aggregate amid near farcical scenes in which they had skipper Lucky Lekgwathi handed a soft red card and the home team awarded two penalties.
There were also reports of intimidation and the arrest of South African journalists covering the match, while the state broadcaster was also barred from covering the match as had been arranged.
Pirates were reduced to 10 men on 28 minutes when Lekgwathi received his marching orders.
The home team were awarded soft penalties by Seychelles referee Bernard Camille, but both were saved by Pirates goalkeeper Senzo Meyiwa, the first from Eric Bokanga and the second Tresor Mputu.
The home side did score on 73 minutes, but could not find the additional goal they needed to win the tie on home soil.
Coton Sport of Cameroun also qualified for the Group phase last Saturday, after holding Stade Malien to a goalless draw in Bamako during the return leg.
The Camerounians go through with a 3-0 win on aggregate, after their large victory at the Roumdé Adjia Stadium during the first leg.
Esperance of Tunisia managed to hold on to their group phase dream courtesy a spot kick converted by Khalil Chammam in the second half aganst JSM Bejaia from Algeria.
The first ended 0-0 and Chammam’s goal ensured that the Tunisian champions stayed on course for another title shot having won it in 2011 and finished as runners-up last season.
Results at a glance:
•TP Mazembe 1, Orlando Pirates 0 ( 1-3)
•Esperance 1, JSM Bajaia 0 (0-0)
•Sere Sports 0, FUS Rabat 0 (1-1)
•Stade Malien 0, Coton Sport 0 (0-3)
•Entente Setif 3, AC Leopards 1 (1-3)
( Leopards advance on 5-4 penalties)
• First leg results in brackets