He built his landmark Vizcaya estate, where he was an early 20th-century resident on Biscayne Bay in the present day Coconut Grove district of Miami, Florida.

Begun in 1910, with architecture and gardens in a Mediterranean Revival style, Vizcaya was his passionate endeavor with artist Paul Chalfin, and his winter home from 1916 to his death in 1925.

James Deering's older brother Charles joined the family business in the 1880s, after attending the United States Naval Academy and serving nine years in the Navy.

By the turn of the century, Deering owned homes on Lake Shore Drive in Chicago, in the countryside near Evanston, Illinois, in New York City, and in Paris.

In 1906, for Deering's work in promoting agricultural technology development in France, he was awarded the Légion d'honneur ("National Order of the Legion of Honour").

Paul Chalfin had attended Harvard, trained as a painter at the École des Beaux-Arts in Paris, and was an associate of renowned decorator Elsie de Wolfe.

In 1910, Chalfin and Deering traveled through Europe together for the first trip of many over the years, in part to collect ideas and begin acquiring art, antiquities, and furnishings for the new Florida estate.

The gardens are notable for introducing classical Italian and French design aesthetics into a subtropical habitat's plant palette and context — a new approach.

While Vizcaya's landscape design style evokes other periods and places, the use of native stone, plants, and light modulation reflected Deering's desire to showcase the indigenous natural beauty.

These endeavors were done with the intent of making Vizcaya primarily self-sufficient, modeled on European estates to compensate for the limited commodities and services of early 1920s Miami.

In this period's personal letters, he expressed the hope that his nieces and nephews would enjoy coming to Vizcaya, so tennis courts, a bowling alley, a billiard room, and a swimming pool were part of the estate to encourage their visits.

Deering never married and attempts to document his personal life and sexuality are inconclusive, though a substantial case has been put forth that he was homosexual, as Chalfin undoubtedly was.