Early in life Tiffany was exposed to the fine craftsmen and designers who conceived and fabricated luxury objects in gold and silver for the firm founded by his father, Charles Lewis Tiffany, in New York City. Tiffany's first creative effort was in painting, beginning in the 1860s. In 1866–67 he traveled to England, Ireland, France, Italy, and Sicily, sketching the places he visited. He first exhibited his work in 1867 at the National Academy of Design and was made a member three years later. During his second trip to Europe, in 1868, he met the Orientalist painter Léon-Adolphe-Auguste Belly and was exposed to the cultures that shaped his career. In 1870 he traveled with fellow artist R. Swain Gifford to Egypt and North Africa, visiting Morocco, Tunisia, and Algeria, gathering subject matter for his canvases.

Tiffany continued to paint, but he made his mark in the decorative arena. There was hardly a medium to which he did not turn, including furniture, metalwork, textiles, pottery, enamels, jewelry, and book design. He became interested in the decorative possibilities of glass in the late 1870s and employed it throughout his career.

Tiffany participated in the Aesthetic Movement, which conferred a new, higher status to the decorative arts. Like other members of the movement, he drew upon historical sources and was attracted to the arts of such exotic places as China, Japan, ancient Greece, Egypt, Venice, India, and the Islamic world. Tiffany likewise responded to the tenets of contemporary British reform movements, emulating the practices of British designer William Morris, and appreciated the fine craftsmanship championed by the Arts and Crafts Movement.