In her first 10 years, Nicholl led the work of the Performance Directorate before taking over as the chief executive in 2010.
During her tenure, London hosted the 2012 Olympics, with Team GB finishing third on the medal tally with 65 medals. This was followed by a second-placed finish at the 2016 Rio Olympics with 67 medals.
"I have shared a very special journey with everyone that has been part of our very successful high performance system over the past 20 years," Nicholl said in a statement.
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"Our athletes are undoubtedly among the very best prepared and supported in the world and I am confident that we can continue to build on the successes of recent Games."
UK Sport said it will begin searching for Nicholl's successor to ensure a smooth transition and handover ahead of the 2020 Olympics in Tokyo.
(Reporting by Hardik Vyas in Bengaluru; Editing by Hugh Lawson)
