Although some fans were excited to see the actor, others were angered, calling his appearance on the panel "inappropriate" as ex-wife Amber Heard was on the same panel promoting her upcoming film, Aquaman.
One fan deemed the appearance "unreal and irresponsible".
Amber Heard and Johnny Depp filed for divorce in May 2016. Ms Heard then filed for a restraining order and alleged he was violent with her.
Many fans expressed their concerns with the two being on the same stage, just minutes apart, given the allegations of domestic violence.
Australian actress Nicole Kidman was seen hugging Heard during the event.
The allegations of domestic violence againmst Heard made his role in the Fantastic Beasts franchise a controversial one.
JK Rowling, author and producer of the films was forced to defend herself for working with Mr Depp.
"When Johnny Depp was cast as Grindelwald, I thought he'd be wonderful in the role. However, around the time of filming his cameo in the first movie, stories had appeared in the press that deeply concerned me and everyone most closely involved in the franchise," her statement read.
JK Rowling then went on to say in light of the allegations, she and director David Yates did consider recasting the role.
Ms Rowling referenced the joint statement made by the former couple, "The agreements that have been put in place to protect the privacy of two people, both of whom have expressed a desire to get on with their lives, must be respected."
To which Ms Heard accused Ms Rowling of taking the statement out of context.
Ms Heard said in court filings her ex-husband was abusive to her throughout their 15 months of marriage, alleging Mr Depp threw a mobile phone at her face during an argument and breaking several objects in her apartment.
Ms Heard was awarded a $7 million settlement from the divorce, all of which she donated to charity.
In the Rolling Stone article, Mr Depp spoke of his depression, relating it to issues in his personal life and financial difficulties. Due to the non-disclosure agreement both parties signed, Ms Heard was not mentioned directly in the article.
Amber Heard was at Comic-Con to promote her new film, Aquaman, which also stars Game of Thrones star Jason Momoa, Aussie actress Nicole Kidman and Patrick Wilson. Ms Heard was seen embracing her co-stars during Comic-Con.
Fantastic Beasts: The Crimes of Grindelwald to be released in November this year and Aquaman in December.
