Warren Gatland believes Wales' clash against South Africa in Washington DC next month will take players "out of their comfort zone".
Wales head coach Gatland has named a 31-man squad for the Springboks encounter, which is followed by two Tests against Argentina in South America.
Gatland has appointed Dragons lock Cory Hill and Cardiff Blues flanker Ellis Jenkins as co-captains for the trip, saying "we are looking forward to seeing how they develop in a leadership role," and rested a number of players who were involved in last summer's British and Irish Lions tour to New Zealand.
The sizeable contingent of absentees include Alun Wyn Jones, Taulupe Faletau, Justin Tipuric, Ken Owens, Dan Biggar, Leigh Halfpenny and Liam Williams, although Gatland has chosen only one uncapped player in Cardiff Blues scrum-half Tomos Williams.
Wales will face South Africa at the 45,500-capacity RFK Stadium, and Gatland said: "It will be a unique experience.
"I will be looking forward to having a different crowd and different atmosphere and being in a city we have not experienced before.
"It will be great for this group of players and take them out of their comfort zone, and we will experience that in Japan 2019 (World Cup). It is how we adapt and respond to that challenge."
Wing George North and back-row forward Ross Moriarty are the only original 2017 Lions selections that make the trip, as Gatland looks to further develop squad depth.