The Amherst Museum features a collection that consists of more than 50,000 objects such as furniture, photographs, clothing, and other artifacts and art pieces. The items in the collection are displayed in numerous rotating exhibits that are held on at different times throughout the year so that visitors can get a chance to view as much of them as possible. The materials in the collection are housed permanently either in the Archives Room or in the Anscombe Collection Storage Building that was built in 2000.

The exhibit collection features about 30,000 objects that include paintings, furniture, prints, woodworking, ceramics, metalworking, and textile working tools. Many of these items bear historical significance pertaining to the Niagara Frontier or Amherst. Among these are furniture from the Timothy Hopkins Family 19th century residence, a pocket watch that belongs to Jacob Snyder, Sterling Amherst Dairy objects, pharmaceutical collection of the Smithers, and other pieces that illustrate the daily life in the early times of Western New York.

The Textile Collection contains 10,000 artifacts dating back to 1740 up to the present. The Museum also contains the Niederlander Research Library & Archives that houses both artifacts and research materials.