Henshaw did the damage in the second half of a dramatic 36-26 defeat against the Springboks at Ellis Park at the weekend and was taken off on a medical buggy.
Ireland team manager Mick Kearney confirmed on Monday that the Leinster-bound 23-year-old has flown home and will consult a specialist.
The absence of Henshaw is a blow to Ireland as they lick their wounds after surrendering a 26-10 second-half advantage to be pegged back at 1-1 in the three-match series.
South Africa have injury concerns of their own, with number eights Duane Vermeulen (elbow) and Warren Whiteley (shoulder), Trevor Nyakane (knock) and Lood de Jager (calf) facing fitness battles ahead of the final Test in Port Elizabeth.
Fly-half Pat Lambie will definitely not play a part as he continues to feel the effects of a concussion suffered in the first match.