Manchester United will come up against their former striker Robin van Persie after being drawn in a tough Europa League group alongside Fenerbahce, Feyenoord and Zorya Luhansk.
Three-times European champions United must negotiate a competitive group if they are to win one of the few titles that has eluded them.
The Premier League side will face 19-times Turkish champions Fenerbahce, who missed out on the Champions League group stage after a 4-3 aggregate defeat by AS Monaco in the third qualifying round.
They are managed by former Netherlands coach Dick Advocaat and include ex-United forward Van Persie who began his career with Feyenoord.
The Dutch Cup holders finished third in the Eredivisie last season. Zorya qualified as Ukraine's fourth-placed team.
Southampton, the Premier League's other representatives, have been drawn alongside Inter Milan, Sparta Prague and Hapoel Be'er Sheva.
Villarreal, beaten semi-finalists last season, meet former European champions Steaua Bucharest, FC Zurich and Osmanlispor.
Group-stage first-timers Dundalk of Ireland meet AZ Alkmaar, Maccabi Tel Aviv and Zenit St. Petersburg, who reached the Champions League round of 16 last season.
The top two teams from each of the 12 groups advance to the round of 32 where they will be joined by the eight third-placed teams from the Champions League group stage.
The final will be played in Stockholm on May 24.
Meanwhile United midfielder Bastian Schweinsteiger is unlikely to play for the Red Devils this season.
Mourinho has used Belgium midfielder Marouane Fellaini and Spaniard Ander Herrera this season and the signings of Paul Pogba and Henrikh Mkhitaryan have pushed Schweinsteiger further down the pecking order.
The 32-year-old Schweinsteiger, who announced his retirement from international football last month, is yet to make a first team appearance this season and has been training with the club's reserves.
"It is very difficult to happen. I'm not saying it's impossible, I'm saying that it's very difficult. We have five players for two positions. It's very difficult that an opportunity will arrive (for him)," Mourinho told reporters.
Mourinho is surprised Bayern Munich have not attempted to bring Schweinsteiger back to the club where he played for 13 seasons before joining United last year.
Bayern chairman Karl-Heinz Rummenigge said players were going to think long and hard before joining United following Mourinho's treatment of Schweinsteiger.
"I thought, when I read some quotes from people at Bayern Munich, they would run to Manchester to bring him back, but no, that didn't happen. I'm quite surprised Karl-Heinz Rummenigge is not here to take him back," Mourinho added.
The 53-year-old Portuguese does not expect the top teams to falter like they did last season and believes clubs vying for the title would need more than the 81 points Leicester City collected to win the Premier League this year.
"I think that more points will be needed to win the competition because many of the top teams under-performed last year, which was amazing for the beauty of the competition," Mourinho added.
The former Chelsea boss also confirmed that United were not planning on bringing in more players in the current transfer window.
"So I think we're going to have a very quiet week, not surrounded by helicopters, waiting for somebody to leave or to arrive, so I am more than happy with the squad I have," he said.