In what turned out to be a dreadful night for the Premier League giants, Manchester United and their noisy neighbours City began their Champions League campaign on a sour note after losing their respective opening games in the group stage against PSV Eindhoven and Juventus on 16 September.
On one hand where Manchester United were shocked by the Dutch club PSV Eindhoven 2-1 at the Philips Stadion in Netherlands, the Premier League leaders Manchester City succumbed 1-2 against the Italian powerhouse Juventus at the Etihad stadium.
United's Memphis Depay, who returned to the club where he made his name, scored an opening goal for his side in 41st minute. But just four minute after United's goal, central defender Hector Moreno scored an equaliser to help Eindhoven level the score in the Group B opener.
PSV laid their cards on the table in the second half, with right winger Luciano Narsingh heading in a beautifully-timed Lestienne cross past David De Gea to find the left hand corner of the United goal. Although Depay impressed throughout the first half, United were rail-roaded by the dogged defence of PSV - who recorded their first Champions League win over United since 2000.
After a goalless first half in the Group D opener, Vincent Kompany pressured Giorgio Chiellini into scoring an own goal to help the in-form City take the lead in the 57th minute. But 13 minutes later, Juventus leveled back after Mario Mandzukic found the back of the net.
City, who registered five straight wins in the Premier League, came close to taking the lead with David Silva and Raheem Sterling. But Gianluigi Buffon produced a superb double-save to thwart first Sterling and then Silva, before beating away an effort from Wilfried Bony.
The Italian giants finally found the winner after former Real Madrid striker Alvaro Morata curled one past Joe Hart in the 81st minute. It was a first setback of the season for Manuel Pellegrini's City, whose home form has bedevilled them in their unsuccessful attempts to progress beyond this tournament's last 16 in the last four seasons.
Apart from their defeats, both United and City also witnessed injury setbacks that is bound to affect their Champions League campaign. United lost Luke Shaw following a crunching tackle by Moreno in the 15th minute while City captain Vincent Kompany was forced off in the 75th minute.
Shaw was wheeled off the field breathing through an oxygen mask following a double fracture that requires an operation when he returns to Manchester. On the other hand, Kompany sustained a calf injury before being replaced by Nicolas Otamendi - who made his debut for City.
United will now lock horns with Germany's VFL Wolfsburg at the Old Trafford on October 1 while City will take on Borussia Monchengladbach at the Borussia-Park in Germany.