He first exhibited his paintings the following year at the Pennsylvania Academy of Fine Arts, after which he sailed to Europe, first joining a colony of American painters who were studying in Düsseldorf, then traveling up the Rhine into Switzerland and Italy.

The precision with which he painted these landscapes won critical praise, and Haseltine was elected an Associate of the National Academy of Design in 1860, and a full Academician in 1861.

Initially the family considered settling in Paris, but in 1867 they moved to Rome, which would for most of Haseltine's subsequent years serve as his home and point of departure from which to produce views of the European landscape.

While his paintings of Capri and Sicily would prove popular with visiting American tourists, Haseltine also traveled and drew in France, Belgium, and the Netherlands, summering in Bavaria and the Tyrol in the 1880s and 1890s.

William's daughter Mildred (Millie), also an artist, married the Roman Prince Ludovico Guardino Carlo Francesco Rospigliosi Pallavicini in Rome in 1904.