The mere fact that Sasuke's stats were that of a chunin, lack experiences fighting fights of such levels to a point of not getting taken out (Against Oro in chunin exam and Itachi after Chunin exam, 2 Kage levels who played with Sasuke and took him out when they were done).
Tsunade was said to be rusty when she was fighting Kabuto but she was still taking hits from his chakra scalpel that would put other ninjas down and chopped him which disrupted his nerve system. The speed Sasuke and Naruto were showing was chunin level speed at most, Tsunade would have better speed than that, and have years of experiences of fighting chunins, jounins and even some Kage level ninjas who would all have speed on the same level as Sasuke and Naruto and higher. Sasuke's speed was 3 while hers was 3.5, it doesn't matter if Sasuke can see the moves, if his body can't react in time.
Tsunade have better stats in taijutsu, ninjutsu, genjutsu, intelligence, strength, stamina, hand seals. Tsunade punched Madara level Katon jutsu with her bare fist with some damage, Sasuke's katon when he's in Shippuden isn't shown to be on Madara level. Tsunade stopped Naruto from using his incomplete Rasengan on her with 1 finger, Kakashi and Itachi were able to grab Sasuke wrist with chidori in mid attack and you don't think Tsunade would do that then 1 hit him?
She is also knowledgeable of Poisons since you need to know about poisons to be able to cure them and she was able to counter all of Chiyo's poisons. Her student of many years Shizune taught Sakura about poisons and sleeping gases when Tsunade was busy with Hokage matter. She can also just summon her slug and have it shoot acid at Sasuke. She stood in front of Naruto ready to take on A and was even keeping up with KM Naruto and A speed as they were moving around, it was when Naruto went full speed that she could only see a "yellow flash".
Sasuke's fire jutsu can get punched into nothingness and his only lightning attack requires him to go to her and jounin level (Kakashi without his Sharingan out) and Kage level (Itachi) ninjas both caught Chidori effortlessly so that wouldn't even work. She was a live when Uchihas were alive and would know more about them than Sasuke himself seeing how her grandfather was Hashirama and granduncle was Tobirama plus she more than likely went to school with them.
