Maharaj ruptured his Achilles in unusual circumstances during last week's Test victory over the West Indies at the Wanderers, falling to the floor as he began celebrating a wicket.
The 33-year-old is now looking at a six-month lay-off, ending his hopes of a stint at Lord's.
Middlesex director of cricket, Alan Coleman, commented: "We are naturally extremely disappointed that Keshav will not be joining Middlesex this year after sustaining this freak injury and we are saddened to hear that he will face a significant absence from playing.
"It goes without saying that everyone at the club wishes him a speedy recovery. For us to lose Kesh so close to the start of the new season is a blow, however he wasn't scheduled to begin playing for us until late April, which buys us a little time to put Plan B into action.
"We will of course keep everyone updated on the situation regarding a replacement overseas player for the coming season."