The Argentina international was diagnosed in 2013 and underwent surgery before moving to Norwich on loan for the remainder of last season - with his last appearance for the Canaries back in April until the game on Monday.
Gutierrez did not make his health issues public until September and since then he has been discharged from hospital and has resumed training - making his comeback as Newcastle beat West Ham 4-1 to advance into the quarter-finals of the Under-21 Premier League Cup.
The former Real Mallorca man captained Peter Beardsley's side and played for 88 minutes before being replaced by Dan Ward in the closing stages.
And, after the game, the 31-year-old took to Twitter to send a message to those who he felt had helped him over the past year - singling out his family, as well as fiancee Alejandra Maglietti and team-mate Fabricio Coloccini.
"Thanks to all the fans for the support that you give through my illness, I am proud to be back. Good game and really happy. Thanks," Gutierrez said.
"Especially thanks to my grandma, mum, dad, Cristina, more, @Eushiguti @el-guti6 @Aye-Chache, coloccini, fermoreno and my love @alemaglietti."
West Ham also sent a message in support of Gutierrez's comeback - tweeting during the game: "Great to see Jonas Gutierrez back playing for @NUFC today. Wishing him all the best, hopefully see him back in the @premierleague soon."
Gutierrez made only two senior appearances for Newcastle last season before a January loan move to Norwich, where he again linked up with former Magpies' boss Chris Hughton, where he featured in four games as the Norfolk club fell out of the Premier League.
But, despite moving on loan to Carrow Road last year, Gutierrez has been assured of a role in Newcastle's first-team by manager Alan Pardew.
"We're pleased to have him back," Pardew said last week.
"Jonas is one of those people who livens up the training ground just with his personality, and obviously his illness has magnified that fact. He hasn't been around much but he's in pretty good shape and we are hoping that in two or three weeks he could be back in and around the first team.
"He's keen to earn his right to play but, like any player here, I have to give him an even keel in terms of access to the first team. It's now up to Jonas but it will certainly be emotional for us and for him when he returns, and we will look forward to it."