The presenter joined the long-running BBC kids programme on January 8, 1999 as Richard Bacon's replacement and has since anchored more than 550 episodes.
"It was a tough decision to make because Blue Peter is a place where you get to fulfil your dreams - and I've certainly done that," said Thomas, 31, today. "But six and a half years is a long time and I feel that now is the time to make way for someone new and to take on fresh challenges."
In his time on the show, Thomas has made more than 300 films including climbing Mount Kilimanjaro and Mont Blanc, freefall parachuting with the RAF, abseiling from a hovering helicopter, escaping from a submarine, competing in the Indoor Athletics championships, diving in Belize and Australia and boxing with Amir Khan.
Blue Peter Editor Richard Marson said: "Simon will be a tough act to follow - a total professional with charm, authority and intelligence - he is one of the definitive presenters for his generation and Blue Peter viewers have shared in all his many triumphs and achievements. We wish him the very best for the future."
The presenter's last episode will air on April 25. Two highlights shows are also planned.