The 22-year-old, who is comfortable in either the second row or the back row, comes in at blindside flanker for Peter O'Mahony, who has failed to recover in time from a hamstring problem, in the only change made by Schmidt.
Henderson came off the bench in Ireland's defeat to England last time out and has amassed eight caps since the autumn of 2012 but Saturday will mark just his second start.
Schmidt admitted that O'Mahony could have been risked but insisted he was impressed with Henderson's cameo at Twickenham.
"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."