Based in New York City since its inception in 1866,[4] the organization's mission is "to provide effective means for the prevention of cruelty to animals throughout the United States.

Starting in 1977, the ASPCA entered into a contract with the New York City Department of Health to receive municipal funding to operate the shelter system.

The contract rendered the ASPCA increasingly reliant on government income rather than private donations, and subject to the effects of annual city budget appropriations.

[12] In 2013, the ASPCA made a $25 million commitment to assist at-risk animals and pet owners in the greater Los Angeles metropolitan area, including a fully subsidized spay/neuter facility in South Los Angeles operated by the ASPCA and a campaign to encourage the fostering of local vulnerable kittens.

Located in Weaverville, North Carolina, the Center provides behavioral rehabilitation to canine victims of cruelty and neglect.

[24][25] In 2021, the Society opened the ASPCA Community Veterinary Center supported by the Alex and Elisabeth Lewyt Charitable Trust, in NYC.

[27] In 2023, ASPCA began releasing an annual report that grades major grocery retailers in the United States on their policies around animal welfare, such as selling cage-free eggs and pork raised without gestation crates.

[29] In 2021, CBS News reported that the ad misled donors, who believed that their financial contributions supported local SPCAs and animal welfare charities.

[30] After the CBS News piece aired, two widely-shared posts on Facebook claimed that the ASPCA's CEO was paid $600,000 annually, and that only three cents of each dollar donated were used "for veterinary supplies and for transporting the animals".

[34] Some of the animal welfare issues the departments work on include ending puppy mills and breed-specific legislation.

[38] ASPCA was among the animal welfare groups that supported the "puppy mill pipeline" bill in New York, which was signed by Governor Kathy Hochul on December 15, 2022.

A common example was displayed in the news in October 2008, when ASPCA was in charge of an investigation involving the slaughtering of a beagle that lived in the Bronx.

[54] ASPCA operates centers where dogs that have experienced abuse or trauma receive treatment and behavior rehabilitation before being cleared for adoption.

As of 2022, the organization has committed $40 million to building and operating the centers, which are located in Weaverville, North Carolina,[55] Columbus, Ohio,[56] with another being developed in Pawling, New York.

The organization piloted the program in 2013 at a temporary site in Madison, New Jersey and reported that approximately 90 percent of the dogs treated recovered enough to be adopted.

[60] Copies of the ASPCA's magazine Animal Protection are digitized and stored at NC State University Libraries.