United captain Fernandes capitalized on two mistakes by West Ham's French international goalkeeper Alphonse Areola to secure the win for Ruben Amorim's team in the sweltering heat at the MetLife Stadium.
Areola was responsible for both of United's goals, and despite Jarrod Bowen pulling one back for the Hammers, the London team never posed a serious threat to the 13-time Premier League champions.
Fernandes struck first from the penalty spot in the fifth minute, confidently sending Areola the wrong way after the Frenchman had unnecessarily pushed Ayden Heaven to the ground after losing the ball.
Fernandes extended United's advantage in the 52nd minute with a smart finish following another error from Areola, whose careless pass from the back went directly to United midfielder Kobbie Mainoo at the edge of the box.
Mainoo provided a pass to Fernandes, who then calmly lifted the ball over the stranded Areola to give United control.
Bowen's clever finish in the 63rd minute narrowed the scoreline, and the England forward forced a solid save from Altay Bayindir in injury time, but United managed to hold on.
"It's great to win, even if it’s just a friendly - we aim to approach every match to prepare ourselves in the best manner and clearly enter the season positively," Fernandes stated to NBC Sports after the win.
"Overall, the game was good; we were very effective with the ball. At times, we could have maintained possession longer, and we rushed it a bit. We need to improve on that... but I believe it was a very positive game for us overall."
United's recent £70 million acquisition Bryan Mbeumo traveled with the squad to the United States but did not make it into the matchday lineup.
Mbeumo may make his debut when United faces Bournemouth in the second round of fixtures in the four-team tournament in Chicago on Wednesday.