The former Wolverhampton Wanderers goalkeeper was signing copies of his new book Why Not Me, which tells the story of his fight against leukaemia.
The 33-year-old was forced to retire from football last year after due to the condition.
Supporters were queueing out the door of the store and out on to Victoria Street, dressed in Wolves shirts with their books and cameras at the ready.
Speaking about the signing, Carl said: "I can’t speak highly enough of the support I have received from Wolves fans, both when I was playing for the club and during my illness.
"Once again they came out to support me at my first book signing at Waterstones and it was great to meet everyone.
"It was nice to chat about my playing days at Wolves, but important also to meet some people who have been affected by serious illness, either themselves or with a family member.
"Part of my motivation for writing the book was to try to show that there is light at the end of the tunnel however tough it gets, and if it helps just a few people who are experiencing what I went through then it will definitely have been worth it."
Written in conjunction with former journalist and head of media at Wolves, Paul Berry, Why Not Me is an inspirational story which looks at every aspect of the most important ‘save’ Ikeme has ever made.
A fan at the signing, 34-year-old Jane Harding, said: "I've always been a Wolves fan so it's great to get the chance to meet Carl today, especially in Wolverhampton.
"The book is really touching, cancer is something that I think affects everyone, and to read his story is upsetting but uplifting to see how he has gotten through it all."
Ikeme will also be heading to the Wolves Megastore on Saturday, December 14, from 10am to 12pm, and Thursday, December 19, from 5pm to 7pm, to present his book to supporters.