Benzema opened the scoring at the Johan Cruyff Arena, netting in the 60th minute after a storming run and assist from Vinicius Jr.
Ajax would go on to level the last-16 first leg through Hakim Ziyech, but Marco Asensio's late winner means Madrid will host the Dutch side in the second leg with a telling advantage.
Only three players have more career Champions League goals than Benzema, and it is an illustrious trio.
Cristiano Ronaldo is tops on the list with 121 goals, followed by Lionel Messi with 106 and Raul with 71.
60 - Karim Benzema is only the 4th player to score at least 60 goals in the Champions League history 🏆— OptaJean (@OptaJean) February 13, 2019
🇵🇹 Cristiano Ronaldo 121
🇦🇷 Lionel Messi 106
🇪🇸 Raúl 71
🇫🇷 Karim Benzema 60
Legends. @Benzema @realmadrid pic.twitter.com/9WzfcTzjO1
It has taken Benzema 110 games to reach the 60-goal mark, with the Madrid forward having lifted the Champions League trophy on four occasions (in 2013–14, 2015–16, 2016–17, 2017–18).
After struggling for form last season, Benzema appears to be back to his best for Madrid this term, and has been especially effective since the turn of the new year.
Benzema has scored eight times already in 2019, level with Lionel Messi for the most goals by a Liga player in all competitions so far this year.
The French forward especially enjoys playing against Ajax in Europe, having been involved in eight goals in six appearances against the Dutch side in the Champions League (four goals and four assists).
Those eight goal involvements are the most Benzema has against any opponent in the Champions League.
Benzema and his team-mates will look to advance to the last eight when they take on Ajax in the second leg in Madrid on March 5.