The character has been the centerpiece of 17 novels from best-selling author James Patterson. The role has been played twice before by Morgan Freeman, so Perry knew he had big shoes to fill.
"My first reaction was, 'No, absolutely not,' because Morgan Freeman had done this role and you don't go behind Morgan Freeman," Perry said. "You can't do it."
"What made me say yes to it was the arc of the character," Perry went on to say. "He's a family man, he goes to work. After the tragedy happens, he becomes someone else, and then he's this lion that's unleashed."
Perry, known to play multiple roles, said he enjoyed focusing on doing just one job on the movie set.
Since he spent much of his time with his new onscreen best friend, fellow writer-director-actor Edward Burns, the two found a creative way to spend their moviemaking down time.
"We started talking about the scripts that we were both working on," Burns said. "He actually got me to write the next script that eventually became my next film. We had a lot of common ground."
Perry said the two challenged each other.
"We both wrote a script in the downtime," Perry said. "Every day we'd go to set, (we would) say, 'I wrote five pages,' 'I wrote six pages,' 'Well, I wrote seven.'"
They had a competition going on to see who would finish their script first. Perry won.
The role of Alex Cross was physical, so in order to run and jump and fight like a top cop, Perry lost 30 pounds.
"Alex Cross" is in theaters Friday.