Although he attempted to improve on the domain's ability to raise taxes by a new land survey, the results were only minor.

The domain also came under increasing criticism from the shogunate for being lukewarm on enforcement of anti-Kirishitan edicts, which cumulated with an order by the council of rōjū that the cadet branch of the Uesugi clan headed by Yamaura Mitsunori be put to death on suspicion of being Kirishitan.

While this was not unusual in itself, Tsunakatsu had fallen ill on the night after he visited his sister and had dinner with Kira Yoshinaka.

Although official histories indicate that he had a perforated ulcer, for the seven days before he died he exhibited all of the symptoms of having been poisoned.

As popular opinion held Kira Yoshinaka to be an arch-villain due to the events of the Chushingura, it was no stretch to imagine that he was behind the poisoning of Uesugi Tsunakatsu, and various publications and dramas promoting this conspiracy had begun to circulate even by the mid-Edo Period.