Nuno Espirito Santo’s side face the 6,370-mile round journey, flying out on Wednesday and back straight after the game on Thursday (17:00 BST KO), before visiting Leicester on Sunday.
“It’s very far but it’s more important to prepare well,” said Nuno.
“It’s a challenge and we’ll embrace it by doing our best.”
He added: “On the flights we’ll make this time useful, trying to rush the recovery of the players with good food.”
The winners face Italian side Torino or Shakhtyor Soligors of Belarus in the final qualifying round before the group stages.
“We are very proud because achieving what we did last season was huge for the club,” Nuno said.
The Portuguese will not rule out making any more signings before the transfer deadline, which is at the exact time the game kicks off.
“The reality is the market is still open so let’s see. When it’s closed and finished, let’s talk about it,” he said.
Italy striker Patrick Cutrone, a £16m signing from AC Milan, and Real Madrid loanee defender Jesus Vallejo could both make their debuts after travelling to Armenia.
Right-back Matt Doherty and striker Raul Jimenez are both available after overcoming injuries.