Most skilled ninja is unfortunately generic.
If you mean power level you’ll get bad answers. Naruto, Sasuke, Hashirama, and Madara are not good ninja, they are powerful fighters with gifts from their bloodline or from Bijuu or both. There is an argument for Hashirama, but he is more of a Superman character than he is a ninja. The Sage of Six Paths should technically be the right answer here, but being Kaguya’s son he also is not exactly fair.
There is a strong argument to be made for Itachi, but his reliance on the sharingan makes for another unfair advantage. He would be a regular Anbu level without it.
Sarutobi, Minato, Tobirama, and Orochimaru are all worthy of consideration. Kabuto also cannot be forgotten because he did some real ninja shit and made the whole last arc possible for Madara/Obito in the first place .
My answer would have been Kakashi for several reasons, but Kakashi himself acknowledges one man as his superior:
Maito Gai is the true answer. He is the greatest of all ninja.