City and Chelsea will first meet at Busch Stadium, home of the St Louis Cardinals, on 23 May, before a second game at Yankee Stadium in New York two days later.
Chelsea chief executive Ron Gourlay said: "The club is excited to be playing a double-header in the US this May and thrilled to be returning to Yankee Stadium.
"We were delighted to take part in the first-ever football game there, and we received sensational support in what was a sea of blue fans inside and outside the stadium that day.
"Spending the week in St Louis and New York also provides a great opportunity for the club to reconnect with our US fans before we head to Asia in July for pre-season.
"America has long been an important place for Chelsea Football Club, and we have seen first-hand the continued rise of the game's popularity."
City spokesman Ferran Soriano added: "Since City's visit to the United States in 2010, our relationship with North American fans has continued to grow.
"We are enthusiastic believers in the development of soccer in the US and have seen first-hand the passion that North American supporters have for the beautiful game. We are delighted to bring City to their doorstep."
All tickets for the St Louis friendly at the 46,861-capacity Busch Stadium sold out within 20 minutes of going on sale.