The Citizens are building towards the Community Shield against Liverpool on July 30, while America played Chelsea in a pre-season friendly on Saturday, suffering a 2-1 defeat to the Blues.
Match preview
Man City won England's top flight for the eighth time last season, finishing one point clear of second-place Liverpool at the summit, but they certainly did it the hard way on the final weekend.
The Citizens were 2-0 down to Aston Villa heading into the final 15 minutes on May 22, but Ilkay Gundogan and then Rodri scored twice in the space of two minutes to level the scores before Gundogan netted his second in the 81st minute, which completed the turnaround and saw Pep Guardiola's side finish above Liverpool.
Man City will face Club America and Bayern Munich in two friendlies this summer before taking on Liverpool in the Community Shield on July 30.
Guardiola's side will then open their 2022-23 Premier League campaign away to West Ham United on August 7, and it will be fascinating to see how the season unfolds for the champions considering that there have been some major incomings and outgoings at the club this summer.
Erling Braut Haaland and Kalvin Phillips have made the move from Borussia Dortmund and Leeds United respectively, while Raheem Sterling, Gabriel Jesus and Fernandinho have been among those to depart.
America, meanwhile, suffered a 2-1 defeat to Chelsea in a pre-season friendly on Saturday; Timo Werner sent the Blues ahead before an own goal from Reece James levelled the scores, but Mason Mount struck late on to hand Thomas Tuchel's side the victory in Las Vegas.
Millonetas signed five new players ahead of their new season, with the standout addition being Uruguay international Jonathan Rodriguez, who arrived in a £5m deal from Al-Nassr.
Fernando Ortiz's side started their 2022-23 campaign on July 3, playing out a goalless draw with Atlas before suffering a 3-2 defeat to Monterrey in their second match one week later; the Mexican giants did manage to pick up their first three points of the season against Toluca on July 14, though, running out 1-0 winners.
America have won their domestic title on 13 occasions, which is a record, placing them one ahead of Guadalajara when it comes to championships, and they will quickly switch their attention back to the league after this match, with their next fixture coming against Tijuana on July 23.
Manchester City form (all competitions):
Club America pre-season form:
Club America form (all competitions):
Team News
Man City will be without the services of Phil Foden, John Stones and Gundogan for their pre-season tour of the United States, with the trio instead set to travel with Man City's Under-23s to Europe.
Guardiola has still been able to select a strong squad, though, with new signings Haaland and Phillips included, while Julian Alvarez is also present, with the striker now moving to the club from River Plate.
Kyle Walker, Ruben Dias, Jack Grealish and Kevin De Bruyne are among those expected to be in the starting side on Wednesday, while youngsters Liam Delap and Cole Palmer will also be hoping to earn some minutes.
Nathan Ake had been strongly linked with a move to Chelsea, but the deal has now collapsed, and he could line up in the heart of the defence here.
As for America, head coach Ortiz will again make full use of his squad for the friendly, as he will also have one eye on the team's next league game with Tijuana.
Guillermo Ochoa is again likely to skipper the team between the sticks, while Henry Martin is expected to lead the line for the Mexican outfit.
Jurgen Damm came into the starting XI for the clash with Chelsea last time out and should retain his spot in a forward area, while there could be a position in midfield for the experienced Jonathan dos Santos.
Manchester City possible starting lineup:
Ederson; Walker, Dias, Ake, Cancelo; Phillips, Rodri, De Bruyne; Mahrez, Haaland, Bernardo
Club America possible starting lineup:
Ochoa; Sanchez, Valdez, Caceres, Reyes; Aquino, Dos Santos; Damm, Fidalgo, Layun; Martin
We say: Manchester City 2-1 Club America
It is always difficult to know exactly what to expect from a team's first pre-season match, especially against a side that have already started their domestic season. America will provide competitive opposition for Man City, but we are tipping the English champions to emerge victorious here.