Zvezda were too strong for hosts Valencia at the Pabellon Municipal Fuente de San Luis on Friday, winning 77-68.
The Serbs improved to a 5-3 win-loss record in Group D that ensured their spot in the next round with two games still to play.
Zvezda were led by Boban Marjanovic and his double-double in Spain.
Marjanovic posted 18 points and 11 rebounds, while former NBA guard Marcus Williams (New Jersey Nets, Golden State Warriors and Memphis Grizzlies) had 17 points of his own in the road win.
Zvezda head coach Dejan Radonjic was understandably pleased with his team's achievement, saying: "Congratulations to my players, the club and our fans. This is a great success for us, going to the top 16.
"We could never dream to be in this situation, qualifying with two games left in the regular season. We are really happy because of that."
Montenegrin Bojan Dubljevic starred for Valencia (2-6), who sit bottom of the group, with a game-high 22 points.
Group leaders Olympiacos were also in action on Friday, accounting for Neptunas 89-79 in Athens.
Olympiacos - now at 7-1 - had four players with double-digit points - Brent Petway (20 points), Bryant Dunston (15), Vassilis Spanoulis (13 points, nine assists) and Oliver Lafayette (12).
Laboral Kutxa saw off Galatasaray Liv Hospital 89-82 in the other Group D game, while Spanish champions FC Barcelona made it eight straight wins by routing PGE Turow 104-65 in Poland.
The Group C leaders had no less than five players in double figures as they preserved their 100 per cent record.
Bostjan Nachbar (18 points) and Mario Hezonja (15 points) were the pick of the bunch.
Group B pacesetters CSKA Moscow also boast an 8-0 record after downing Cedevita 97-79.
CSKA made six three-pointers in the first quarter and another six in the second as they powered past the Croatians in Moscow.