Kareem Omoloja (7'), Tirthankar Sarkar (11') and John Chidi (62') were on target for Mohammedan while Joseba Beitia (25') and Salvador Perez (70') scored for the Green and Maroons.
Antonio Vicuna made just one change to the Mohun Bagan starting XI which defeated NBP Rainbow AC 1-0 with Alexander Romario replacing Britto PM on the right flank.
Mohammedan Sporting started the match on the ascendancy and took a two-goal lead within 11 minutes of the match.
Satyam Sharma attempted a long-range shot in the 7th minute from the edge of the box but Debjit Majumder fisted it out for a corner. Soon after, Tirthankar Sarkar sent a curling corner into the box and Kareem Omoloja found the back of the net from the resultant melee.
Tirthankar doubled the lead in the 11th minute with a world-class finish from the edge of the box after Musa Mudde intercepted the ball in the midfield and forwarded a through ball.
Joseba Beitia pulled one back for Mohun Bagan in the 25th minute from a picturesque free-kick from 22 yards. The Spaniard had himself won the free-kick after he was brought down just outside the box.
Beitia could have equalised in the 35th minute when he attempted a long ranger from the edge of the box but Priyant Singh pulled off a quality save to deny him.
Mohammedan should have doubled their lead in the 53rd minute when John Chidi found himself one-on-one with Debjit Majumder from a counter-attack but he failed to find the back of the net.
Chidi made up for the missed chance by finally scoring in the 62nd minute. Tirthankar took a shot at goal from the edge of the box which Debjit stopped but Chidi sent the ball home from the rebound.
Vicuna left on stone unturned to engineer a comeback after his side concede the third goal as he introduced Spanish striker Salvador Perez. The change proved to be an instant hit as the Spaniard pulled one back for Mohun Bagan with a perfect header off Beitia’s free-kick in the 70th minute.
Mohammedan Sporting could have further increased their lead had Vanlal Biaa Changte been a bit more clinical in front of the goal.
Mohun Bagan's title hopes suffered yet another setback with the defeat while the Black Panthers remain in the title hunt after the three points.