Taekwondo competitor Zakia Khudadadi and track athlete Hossain Rasouli were due to arrive in Japan on Tuesday.
Khudadadi was set to become the first woman to represent Afghanistan at the Paralympics.
The International Paralympics Committee confirmed on Monday that, with the Taliban takeover, the two athletes would no longer be able to travel to Japan.
“Regrettably, NPC (National Paralympic Committee) Afghanistan will no longer participate in the Tokyo 2020 Paralympic Games,” IPC spokesman Craig Spence said.
“Due to the serious ongoing situation in the country, all airports are closed and there is no way for them to travel to Tokyo.”