"It was irresponsible for Mr Cruise to use his movie publicity tour to promote his own ideological views," it said.
Cruise called psychiatry a "pseudo science", after NBC host Matt Lauer questioned the 42-year-old's stance against anti-depressant drugs.
The actor criticised Brooke Shields for taking drugs for post-natal depression.
The APA, which represents more than 36,000 physicians specialising in the diagnosis and treatment of mental illness, challenged Cruise's assertion that psychiatry lacks scientific merit.
"Rigorous, published, peer-reviewed research clearly demonstrates that treatment (of mental illness) works," said a statement released by the association.
"It is unfortunate that in the face of this remarkable scientific and clinical progress that a small number of individuals and groups persist in questioning its legitimacy."
It raised concerns that the Hollywood actor's remarks could "deter people with mental illness from getting the help they need".
Cruise, who is currently promoting the Steven Spielberg blockbuster War of the Worlds, is a follower of the Church of Scientology which is against psychiatric medicine.
On Friday, the actor entered a heated discussion with Today host Matt Lauer, when he suggested some people could benefit from drugs such as Ritalin, which is prescribed to children with Attention Deficit Hyperactivity Disorder (ADHD).
"You're glib. You don't even know what Ritalin is," Cruise told Lauer on Friday night's show.
"Psychiatry is a pseudo science," he said. "You don't know the history of psychiatry - I do," he added.
War of the Worlds is set to open across the US and UK later this week.