Oxlade-Chamberlain put in a lively performance in Wednesday's international friendly in Miami, which ended 2-2 and with both sides reduced to 10 men.
However, the Arsenal youngster had to be withdrawn just after the hour mark following a challenge from Carlos Gruezo that left him limping.
And England have now confirmed the severity of the injury, although there is no indication as to how long he will be sidelined or the impact it has on his hopes of featuring at the upcoming FIFA World Cup.
A post on the official England Twitter account read: "(Oxlade-Chamberlain) sustained a medial knee ligament injury against Ecuador. The team medics are continuing to monitor and treat injury."
Oxlade-Chamberlain's participation in England's opening group game in Brazil against Italy a week on Saturday is now in serious jeopardy.
The 20-year-old was playing in his first match since featuring in Arsenal's 3-0 Premier League victory at Hull City in April, when he suffered a groin injury.
