O'Mahony picked up a hamstring injury in the defeat to England and hasn't recovered with Schmidt turning to Henderson at blindside flanker in his absence.
Henderson's only other start came against the USA over the summer and Schmidt believes this could be the start of something special for the 22-year-old Ulster flanker.
"He's in good shape, he's a good athlete, and we felt he made quite an impact when he came on against England," said Schmidt.
"He's got a really good future at both international and the provincial scene. There was a decent temptation to make a few more changes.
"We think there are players out there who have earned an opportunity but we have to balance that with continuity that we've had.
"Some players had a weekend off last week with their provinces and if they miss two weekends it wouldn't be the best preparation for France.
"I think the team we have selected reflects the respect we have for Italy."
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Guinness PRO12 Ulster News
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