With the Americans placed 11th in the FIFA rankings and Bolivia 84th, the USA have a good opportunity to take the first step toward advancement to the knockout round.
Securing victories over Bolivia and Panama, ranked 43rd, would guarantee advancement for the hosts, irrespective of the final group match outcome against 14th-ranked Uruguay.
However, the American squad harbour larger ambitions than just making it to the knockouts.
"For me, it's getting past the quarter-final," midfielder Tyler Adams said.
"We need to - in a pressure situation - win in a knockout. That's going to measure a lot of our success."
Scepticism around coach Gregg Berhalter's leadership ability was heightened following an unconvincing run-up to the tournament and a crushing 5-1 defeat by Colombia.
However, a 1-1 draw with Brazil, one of the tournament favourites, relieved some of the mounting pressure.
This year's Copa America features 16 teams, including 10 South American sides and six CONCACAF (North and Central America and the Caribbean) invitees.
"When you talk about some of the most watched games, I think aside from the World Cup, you look at the Copa América, right?" USA defender Mark McKenzie said.
"You talk about countries that have won multiple World Cups, in Uruguay and Argentina and Brazil.
"You have the opportunity now to step into this tournament and go head-to-head with them. Ultimately, it's usually a South American tournament and now we have the opportunity to play against them."
Bolivia, currently in the midst of a transition phase, has appointed former Brazilian player and Copa América 1999 winner, Antonio Carlos Zago, as their new head coach.
Although they face a daunting task having won only one of their last 30 Copa America matches, they will be looking to cause an upset against the higher-ranked Americans.
"The most important thing is for us to compete," Zago said.
"We have to try to play on an equal footing with the big teams in terms of intensity and physicality."
