Trimble was a key member of the Ireland side that won the Six Nations earlier this year and has earned 57 caps for his country, scoring 16 tries.
However, he will be unavailable for the November Tests with South Africa, Georgia and Australia at the Aviva Stadium after sustaining ligament damage in his toe during Ulster's Pro12 clash with Glasgow Warriors.
In a further blow to Ireland coach Joe Schmidt, Trimble's team-mate and centre Luke Marhsall is also out with medial ligament damage suffered while playing for Ulster's 'A' side Ulster Ravens versus Yorkshire Carnegie.
Marshall made his debut for Ireland in the Six Nations clash with Scotland in February last year.
A statement on Ulster's official website read: "Andrew Trimble suffered significant ligament damage to his great toe playing in the Pro12 game against Glasgow Warriors.
"Ulster Rugby, in conjunction with the national medical staff, will seek second opinion on the management of the injury, however it’s is expected that he will be out of rugby for a period of months.
"Luke Marshall sustained a medial ligament injury to his left knee playing for the Ravens against Yorkshire Carnegie on Saturday.
"He is expected to be out of rugby for six weeks."
Ireland face South Africa on November 8.