The charity says Britain's premier dog show concentrates too much on animals' appearance rather than their welfare and temperament.
"Intentionally breeding deformed and disabled animals is morally unjustifiable and it has to stop," said its chief veterinary adviser Mark Evans.
"Dog shows using current breed standards as the main judging criteria actively encourage both the intentional breeding of deformed and disabled dogs and the in-breeding of closely related animals," Evans added in a statement.
The charity will not attend Crufts next March nor the Discover Dogs show in November. It called for more research into illnesses and causes of death linked with pedigree dogs.
It has ordered a review of dog breeding, which is expected to report back later this year.
Preliminary recommendations from the review call for a radical change in the requirements for pedigree dog registration and breeding strategies.
"We want to see the emphasis shifted away from arbitrary appearance, so that health, welfare and temperament are considered first and foremost," Evans said. "All those who benefit from pedigree dogs have a collective responsibility to solve what is now a very serious and totally unnecessary animal welfare problem."
The organisers of Crufts, the Kennel Club, described the RSPCA's comments as "unhelpful".
Club spokeswoman Caroline Kisko said in a statement that "the club invests a great deal of time, money and care into the area of pedigree health".
A health survey it conducted found that 90 percent of pedigree dogs do not suffer from illnesses that affect their quality of life.
"Dog shows are fundamentally designed to reward those dogs that meet a particular breed standard, which is the blueprint for a healthy dog," Kisko said.
"The Kennel Club is continually working to ensure that this objective is achieved by regularly reviewing breed standards and ensuring that judges are educated so that dogs displaying visible health problems will not win at dog shows.
"The fact that the RSPCA continues to make such unhelpful statements with regard to the health of pedigree dogs is extremely regrettable but we will continue to endeavour to work with them despite their stated position -- for the benefit of dogs."