The Frenchman found the bottom corner inside ten minutes of the match, his 12th goal for the club since his summer signing.
Mbappe is yet to win the Champions League although there is a sense he could finally do so with the record 15-time winners Madrid.
Silverware aside, the forward's goal against Atalanta was his 50th in what is just his 79th appearance in the competition across spells at Monaco, Paris Saint-Germain and Los Blancos.
Mbappe has reached this tally at the age of 25 years and 356 days, which makes him the second-youngest to ever do so.
Only Lionel Messi has bettered him as the Argentine hit 50 goals in the Champions League aged 24 years and 284 days.
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He did so in 2012, with the footballing legend totalling 129 goals in the competition across 163 appearances with Barcelona and PSG.
Unfortunately for Mbappe, his night was cut short as he went off with what appeared to be an injury.
The 25-year-old was substituted by Carlo Ancelotti and replaced by Rodrygo in the 36th minute as he made his way off the pitch.
To make matters worse for Real, Atalanta equalised just before half time through a penalty by Charles De Ketelaere.
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Mbappe's appearance was his 22nd for Madrid following his free transfer from PSG.
He scored his first Champions League goal for the club in their 3-1 win against Stuttgart in the opening week.
The forward then went four European matches without scoring before his neat finish on Tuesday night.
Madrid later scored two more goals from Vinicius Jr and Jude Bellingham before Ademola Lookman pulled one back for Atalanta.
The Reigning champions have shocked fans with their progress in the Champions League this season amid three defeats.
Lille surprisingly beat them first before back-to-back losses came against AC Milan and Liverpool.
Madrid currently look set to finish in the play-off spots rather than the top eight, which would take them through to the last 16.