The bird, named Millicent, took flight from her nest at the RSPB's Loch Garten Reserve, near Inverness, at 4.46pm on Saturday.
The landmark fledgeling is the oldest of three chicks hatched by resident female EJ and her partner Odin this season. Fellow females Seasca and Druie are expected to leave the nest for the first time in the next few days.
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Osprey centre manager Richard Thaxton said: "This marks a milestone . Millicent was the first to hatch this season and the biggest of the three sisters so we were confident she would be first to leave, and become our 100th fledgeling."