The veteran striker met with Cottagers boss Roy Hodgson at the club's training ground to discuss his future and has decided to move on after four and a half years.
McBride's final season at the club looked likely to be ruined by injury, only for the forward to return to play a crucial role in Fulham's remarkable escape from relegation from the Premier League.
The former USA international forward told the club's official website: "After much consideration with my family, we have decided to leave Fulham after four and a half fantastic years.
"I have always stated my intention to return to America at some stage and this seems like the right moment in my career to move on.
"I would like to take this opportunity to thank the club, the chairman, the staff and wonderful fans for all their support, on and off the pitch, during my time at Fulham.
"I take great pride in the fact that my last appearance for Fulham saw the club maintain their Premier League status.
"I leave with some wonderful memories from my time at Fulham and the club will always be in my heart.
"I would like to wish the club, Roy Hodgson and my team-mates every success for the future."
Hodgson hailed the role played by McBride in the club's survival, after they had looked doomed to relegation at one point, and revealed he had hoped the player would stay in west London for another year.
"His attitude is second to none - Brian is a true pro in every sense of the word. On behalf of the club I would like to thank Brian for his valuable contribution over the last four and a half years.
"I would personally like to thank him for his contribution and assistance to me and my staff over the last five months. His performances helped us retain our Premier League status.
"The club would have liked Brian to stay for at least another year but respect the decision he has made with his family, and I wish him every success for the future."