The third seed Bhupathi-Mirny player lost the close championship match 6-7 (6), 4-6 to the second seed Canadian-Serbian combination in one hour and 21 minutes.
Bhupathi and Mirnyi, who came into the prestigious tournament after winning the Paris Masters, had reached the final for the first time together.
Bhupathi had earlier ended runners-up at the Tour Finals in 1997, 1999 and 2000 with Leander Paes.
He had qualified for the elite eight-team competition with Mirnyi in 2003 and 2004 but could never crossed the group stage.
Bhupathi and Mirnyi would have liked to end their partnership with year-end championship victory.
Bhupathi has announced he will yet again team up with Paes for the initial part of the 2011 season while Mirnyi will pair with Nestor.
They had reunited for the 2010 season for the first time since 2004. They reached five finals, including four ATP World Tour Masters 1000 event and won the lone title in Paris.
In the final on Sunday, Bhupathi and Mirnyi had two break chances in the opening set but could convert none and that cost them as they went to concede the lead by losing the tie-breaker.
Nestor and Zimonjic though did not miss out on their chance as they broke Bhupathi and Mirnyi in one of the two chances in the second set and maintained the lead to pocket the title.