The Premier League champions have started a new era following the retirement of Sir Alex Ferguson, who stepped down from his role after accumulating 38 trophies in 26 years at Old Trafford.
"The most radical change is at Manchester United because Ferguson has been there for so long," Cazorla told the official Arsenal magazine.
"It will be a little difficult at the start for a new manager but I don't think it influences too much in terms of being an advantage for other teams. There are great managers at those clubs and I'm sure [the title race] will be just as difficult."
Cazorla is currently representing Spain in the Confederations Cup in Brazil.