Welshman North suffered a hamstring tear in Tuesday's 31-31 draw with the Wellington Hurricanes, while Irishman Henshaw tore a pectoral muscle in the first half of the match.
Both will return to Europe for further treatment this weekend, the Lions said in a statement on Thursday.
North was one of the standout players in the tourists' series victory over Australia in 2013 but has suffered a series of concussions and a dip in form since.
He was given a chance to shine in the crunch match against the Maori All Blacks, where coach Warren Gatland was expected to unveil his test side, but was replaced after his mistake led to a try for the home side.
The 25-year-old subsequently missed out on the team for last week's first test against New Zealand, which the Lions lost 30-15, and sustained the injury after scoring a try against the Hurricanes.
Henshaw, who scored a try when Ireland beat New Zealand in Chicago last November, lasted only 20 minutes of Tuesday's match before being forced off the pitch.
He had in any case struggled to make a case for a test spot on the tour with coach Warren Gatland preferring rugby league convert Ben Te'o and Welshman Jonathan Davies in the centres for last weekend's clash against the All Blacks.
With only two tests remaining in the 10-match tour and plenty of cover in the backline, Gatland is unlikely to name any replacements unless there are further injuries in Wellington on Saturday.
(Writing by Nick Mulvenney in Sydney; Editing by Ian Ransom)