With practically his first touch of the match, the Portuguese forward turned home a stunning ball from international teammate Bruno Fernandes to open his account in this season’s competition, with the strike coming 12 years and 132 days after his last United goal in the Champions League.
Ronaldo now has 135 goals in competition, 15 ahead of Lionel Messi in second.
It had already been an eventful evening for Ronaldo in the Swiss capital of Bern after a wayward shot during the pre-match warm up struck a security guard who was near the stands.
Ronaldo quickly hopped over the advertising boards to go and check on the guard, who was being looked after by other stadium personnel.
On the pitch, things got slightly more complicated for United later in the first half after defender Aaron Wan-Bissaka was shown a straight red card for a clumsy lunge on Christopher Martins.
Young Boys started the second half on the front foot and their extra man advantage soon began to show, as United was forced to defend wave after wave of attacks from yellow and black shirts.
The home side got the equalizing goal its dominance deserved, as Nicolas Ngamaleu poked home a Silvan Hefti deflected cross 20 minutes into the second half.
However, despite dominating for the remainder of the match, it took Young Boys until the final kick to find a winner in front of a raucous home crowd.
Jesse Lingard’s sloppy back pass in the dying seconds allowed Theoson Jordan Siebatcheu to get in behind United’s defense and calmly slot the ball past David de Gea.
The crowd inside the Wankdorf Stadium erupted and the celebrations of the historic win will go likely go on well into the night.