uwsgi + nginx + flask: upstream prematurely closed

As mentioned by @mahdix, the error can be caused by Nginx sending a request with the uwsgi protocol while uwsgi is listening on that port for http packets.

When in the Nginx config you have something like:

upstream org_app {
    server              10.0.9.79:9597;
}
location / {
    include         uwsgi_params;
    uwsgi_pass      org_app;
}

Nginx will use the uwsgi protocol. But if in uwsgi.ini you have something like (or its equivalent in the command line):

http-socket=:9597

uwsgi will speak http, and the error mentioned in the question appears. See native HTTP support.

A possible fix is to have instead:

socket=:9597

In which case Nginx and uwsgi will communicate with each other using the uwsgi protocol over a TCP connection.

Side note: if Nginx and uwsgi are in the same node, a Unix socket will be faster than TCP. See using Unix sockets instead of ports.

In my case, problem was nginx was sending a request with uwsgi protocol while uwsgi was listening on that port for http packets. So either I had to change the way nginx connects to uwsgi or change the uwsgi to listen using uwsgi protocol.

Change nginx.conf to include

sendfile        on;
client_max_body_size 20M;
keepalive_timeout  0;

See self answer uwsgi upstart on amazon linux for full example