The 31-year-old will meet Vargas in Birmingham hoping a convincing display will get him a world title fight before the end of the year.
Vargas, who is based in Toronto, Canada, is ranked #10 in the WBA division.
Khan fought for first time in almost two years, and won for the first time since 2015, when he demolished another fighter from Toronto, Canadian Phil Lo Greco in 39 seconds in April.
“One of my aims this year was to be as active as possible so I’m very happy to get back in the ring again so soon against Samuel Vargas,” said Khan at the announcement of the bout.
“Vargas is a tough and well-schooled fighter who has shared the ring with some top welterweights including Danny García and Errol Spence Jr.”
Vargas ended up with him on the wrong end of a knockout against both García and Spence.
“I have to get past Vargas before looking at the biggest challenges going forward. I’m not going to be taking Vargas lightly because I know he will be coming with everything on September 8.”
Vargas, whose last fight ended in a draw with Mauro Godoy in February, said he would put up a much better performance against the 2004 Olympic silver medallist than Lo Greco had done.
“I have been granted more than enough time to properly prepare for Amir and you will see the best Samuel Vargas to date,” said Vargas.
“Mark my words, we might both be from the same city and county but I am nothing like Phil Lo Greco, that’s a guarantee – I’m going to give Amir hell,” added the 29-year-old.