"It is with great sadness that the time has come for me to hang up my playing boots," Fabregas said on Saturday in a statement posted to Twitter.
"From my first days at Barca, Arsenal, Barca again, Chelsea, Monaco and Como, I will treasure them all. From lifting the World Cup, the Euros, to winning everything in England and Spain and nearly all the European trophies, it has been a journey that I'll never forget."
Fabregas spent much of youth career at Barca before switch to Arsenal, where he made his senior debut and went on to become a club icon as he made 303 appearances between 2003 and 2011.
The midfielder then returned to Barca to rejoin the crop of players he left at youth level, including Lionel Messi and Gerrard Pique, and helped the club to win LaLiga in 2013 as well as two Spanish Cups.
Meanwhile, Fabregas excelled at international level with Spain, in which he went on to win 110 caps and was a key part of the side that won a remarkable two Euro titles the either side of their victory at 2010 World Cup.
"It's not all sadness though as I'm now going to cross the white line and start coaching the B and Primavera [youth] teams of Como 1907. A club and a project I couldn't be more excited about," he added.
"This charming football team won my heart from the first minute and came to me at the perfect time in my career. I will grab it with both hands.
"So after 20 incredible years full of sacrifice, dedication and joy, it's time to say thank you and goodbye to the beautiful game."
Information from Reuters contributed to this report.