Ajax will face Dinamo Zagreb in the first round of the UEFA Cup after again failing to qualify for the Champions League.
In other marquee matchups, Bayern Munich plays Portuguese side Belenenses, Tottenham takes on Anorthosis of Cyprus and Anderlecht faces Rapid Vienna.
A total of 80 clubs were in Friday's draw, with the two-legged matches played Sept. 20 and Oct. 4. The winners of the 40 matches will enter the draw for the group stage, to be made Oct. 9 in Nyon, Switzerland.
Ajax, which has won the European Cup four times, lost to Slavia Prague in Champions League qualifying on Wednesday, dropping it into the UEFA Cup, European soccer's second-tier competition.
"It is a very tough draw for us. We have some luck, I think, because we play the first match away," Ajax technical director Martin Van Geel said, adding that he was not familiar with the Dinamo players.
"Not at this moment, I have to look at that," Van Geel said.
Ajax won the UEFA Cup in 1992. Dinamo also lost in Champions League qualifying, to Werder Bremen.
Bayern Munich is another club more familiar with the Champions League, but only qualified for the UEFA Cup after finishing fourth in the Bundesliga. Bayern has also won the European Cup four times, the last in 2001, but it also lifted the UEFA Cup in 1996.
Tottenham and Anderlecht have also hoisted the UEFA Cup trophy in the past. Turkish side Galatasaray, another former champion, was drawn to meet Sion of Switzerland.
Tottenham lost in the semifinals last year to Sevilla, which went on to win the competition for the second straight year, and Spurs are still feeling the effects of that loss.
"Last year was a big frustration for us," Tottenham's sporting director Damien Comolli said. "Everyone said that the team which won our match would go on to win the competition, and that's what happened."
Two-time defending champion Sevilla was also in the draw as its Champions League second-leg qualifying match with AEK Athens was postponed because of the death of its midfielder Antonio Puerta and the devastating forest fires in Greece.
Sevilla leads 2-0 ahead of the rescheduled match on Monday in Athens, with the winner advancing to the Champions League group stage and the loser playing Salzburg in the UEFA Cup.
The 40 teams that advance from the first round will be put into eight groups of five. Each side plays four games _ two at home and two away.
The first three clubs in each group advance to a knockout round, where they are joined by the eight third-place clubs from the Champions League group stage.
The competition continues on a knockout format until the final on May 14 at the City of Manchester Stadium in England.