The loss, coming after a spate of three draws from the first three games, cost Anand quite dearly as from his joint lead, the Indian was pushed to the last spot.
With just two rounds remaining, Caruana emerged as the sole leader with 2.5 points, a half point ahead of Kramnik and Gelfand while Anand on 1.5 point is currently at the bottom of the tables.
Anand's main chances now depend upon his final white game against Kramnik in the last round. The tide seems to have turned heavily in favour of Caruana, who finished second behind Anand in the just concluded Grenke Chess Classic.
Playing white, Anand faced the Moller variation in the Ruy Lopez and yet again Caruana came up with another opening idea and equalised successfully.
The Italian is fast turning into a player to follow when it comes to creating new ideas in a chess opening, every now and then coming out with some exemplary new ideas.
The middle game remained complicated but, understandably, Anand was playing for a win and went on pushing for an advantage that was not forthcoming.
As it happened, the world champion sacrificed a rook for a minor piece and apparently had decent compensation but his position worsened as the game progressed.
Caruana was in his element in successfully going for an exchange spree resulting in a winning endgame in very quick time.
After six draws in the first three rounds, Caruana's victory also turns out to be the first decisive game of the tournament and although it looked both games might be decisive in the fourth round, Gelfand survived by the skin of his teeth.
Kramnik turned out to be the better judge of his position against Gelfand from a Catalan opening. The Russian came up with a piece sacrifice resulting in a tactical melee but soon both players started to make serious mistakes. The drawn result was justified in the end.