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United came into the contest on the back of a 5-0 hammering by their bitter rivals Liverpool but goals from Ronaldo, Edinson Cavani and Marcus Rashford sealed a comfortable win.
Liverpool romped to a stunning 5-0 victory at Old Trafford that leaves Ole Gunnar Solskjaer's future in serious doubt.
After a poor first-half display, with Atalanta taking a 2-0 lead in at the break, Ole Gunnar Solskjaer's team turned the game -- and possibly their season -- around with a thunderous performance.
The result also ended United's record 29-game unbeaten away run in the league as they collapsed in a frantic five-minute spell in the closing stages.
On the night he set the new record for the most appearances in the competition, the 36-year-old delivered the killer blow to save his manager Ole Gunnar Solskjaer from another disappointing result.
The 21-year-old England international has started only two of Manchester United's five Premier League games since his move from Borussia Dortmund.
The Portuguese superstar dedicates his Manchester United return to former boss Alex Ferguson.
Kane, who has been linked with a move to champions Manchester City all summer, came on in the second half and missed a great chance.
The Belgium international is in line to feature against Arsenal in the Premier League on Sunday.
Paul Pogba also starred with four assists - one more than he managed in the whole of last season in the league - to help United run riot in front of their first full crowd in 17 months.