Messi's exit, following that of Cristiano Ronaldo from Madrid in 2018 -- and coupled with Spanish teams' failure to win the Champions League in the last three years -- has led some to question the current level of the two Clasico giants.
"For me, it's still the same. It remains the best match that exists in football," Benzema told ESPN's Julien Laurens in an exclusive interview. "It doesn't matter about the players who are there, who have left or who will join. Real-Barca is historic. The names change but before there was [Zinedine] Zidane, Ronaldinho, Ronaldo, [Samuel] Eto'o. Real-Barca will always be Real-Barca."
Real Madrid are top of LaLiga, but lost their last game away at Espanyol, while Barcelona have only won once in six matches in all competitions, including a 2-0 defeat to champions Atletico Madrid before the international break.
That run of form risked costing Koeman his job before the coach eventually received the backing of president Joan Laporta.
"There's never a good moment to play [them]," Benzema said. "A team like Barca or any top team, they can have a poor game and then bounce back again. It's a match that we can't take lightly, even if they haven't played well so far."
Benzema goes into next weekend's Clasico as LaLiga's top goalscorer (nine) and assist provider (seven) so far this season, a vein of form that has seen him among the favourites to win France Football's 2021 Ballon d'Or for the world's best player next month.
"It's been a dream since I was young and also a motivation," Benzema told ESPN. "The Ballon d'Or represents the best players in the world and [it's great] to be on the list... if you count who's on there, it's very satisfying. It's always been an objective."
The 33-year-old forward said he believes he's "not too far" from winning the award.
"Yes, you could say that," he said. "What I've done for the last three to four years, to continue to perform at a high level. When I'm playing I don't think about the Ballon d'Or. I think about helping the team win, providing a spectacle.
"The Ballon d'Or comes as a result of that because it's more of an individual focus, but it's all about the collective."
Benzema was on the scoresheet alongside Madrid target Kylian Mbappe as France beat Spain 2-1 to win the UEFA Nations League final on Sunday, and he has made no secret of wanting their strike partnership to continue at club level.
"He's great to watch, I like him a lot and, in the games, it's getting better and better," Benzema told ESPN. "If we look at the previous game, we're finding each other better and better, he knows what I want and vice versa... Let's see [if we play together at Madrid]. Now it's great that we play together in the French national team but afterwards in terms of Real, let's see in the future."