Somdev, ranked 78, had won the first set 7-6 (3) in an hour and seven minutes and immediately after this, Del Potro took a medical timeout due to pain in his left wrist.
The Argentine second seed found it tough to continue and conceded the match.
Somdev had lost 4-6 4-6 to Del Potro last year at this very event in the pre-quarterfinals.
Somdev has competed against the legends of the game, Rafael Nadal, Roger Federer and Novak Djokovic but haven't won against any of them, although he fought well against all these multiple Grand Slam winners.
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He lost to Nadal in 2011 at Indian Wells Masters in two close sets and the same year he had lost to Federer at this very Dubai event.
Last year in his second meeting against the Swiss legend at the Roland Garros, he suffered a tame defeat in the second round.
Before today's match, his one of the biggest wins were against Croatia's Marin Cilic (world number 15) and Ivo Karlovic (world number 25) in 2009 and against Cyprus' world number 22 Marcos Baghdatis (world number 22) in 2010.
Somdev was well prepared coming into this tournament as he had won the Delhi Open Challenger tournament on Suday. He had reached the semifinals of the Chennai and Kolkata events in the preceding weeks.
The Indian traded a break with Del Potro before pushing the match into tie-breaker. He kept hitting it on the backhand of the Argentine, inducing unforced errors from his big-bodied rival.