Mooney, who top-scored for champions Australia in the final of the T20 World Cup against South Africa last month, won the toss and elected to field against Mumbai Indians, who amassed 207-5 at the DY Patil Stadium near Mumbai.
Leading Gujarat's chase, Mooney faced three balls before injuring her left knee as she turned while running.
In her first major captaincy role, she had to be helped off the field, and Gujarat were all out for 64 in 15.1 overs, succumbing to a massive defeat.
Sneh Rana, Mooney's deputy at Gujarat, could not immediately provide an update on the extent of the Australia's injury.
"We are still to be updated by the physio," Rana said even as she promised Gujarat, who face UP Warriorz on Sunday, would bounce back.
"We will keep our head high. The tournament has just started. We'll come back stronger."
Mooney's national team opening partner Alyssa Healy leads UP Warriorz, while Australia captain Meg Lanning is in charge of Delhi Capitals.
