Great question — answering as the UphillTech team:
It's not confirmed exactly how he got defeated just yet. And please correct me if I am wrong, but according to Amado, Isshiki dropped his guard and got attacked suddenly. Also, we don't know if he is one of the most powerful in the Otsutsuki Clan, but out of all revealed members, I say he is THE most powerful, I mean, even Naruto and Sasuke had a hard time against him, as Jigen too.
Full answer by UmbraRabbit: https://anime.stackexchange.com/a/61933 (CC BY-SA 4.0).
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