Mohammedan Sporting who led 1-0 at half-time scored through Josimar (32nd, 89th) and substitute Ajay Singh (71st).
While Sporting Clube de Goa, who were reduced to 10 men in the dying minutes when Boima Karpeh was sent off for pushing Israil Gurung, pulled one back through Boima Karpeh in the 58th minute.
The win takes Mohammedan Sporting to sixth place with seven points from six matches. Sporting Clube de Goa remained on fifth place with 10 points from six matches.
Visitors named an unchanged side that had won the last match.
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Both the teams started cautiously with the play confined to midfield initially.
Sporting Clube de Goa who created more scoring chances found the net first, but Rowllin Borges was pulled off side by the referee.
Mohammedan Sporting slowly tried to take control of the proceedings with Josimar and Tolgay Ozbey combining well upfront with the former finding the net in the 32nd minute as he made a swift run inside the box off Penn Orji through pass and placed the ball at the far corner of the net.