Orlando Giannini was born in Cincinnati, Ohio on March 3, 1860, the son of a sculptor. In June of 1876 he left school to practice modeling and carving. And on November 11, 1876 he began his professional career at the John Muelier Stone Yard in Cincinnati. At about the same time Orlando joined his brother Arthur and eight other gentlemen in the formation of a club called the XentricX. On the evening of October 28, 1876, at 60 West 4^th Street, in Cincinnati, the club held its’ first meeting “for the purpose of furthering the ties of friendship which already bound them.” The club held annual meetings every October 28^th at least through 1885, each reporting to the other members a summary of their lives for the past year. Between 1876 and 1880 he worked as a stone cutter for several firms in the Cincinnati area. Besides the Muelier Stone Yard, Giannini also worked at the Isaac Graveson Stone Yard, the O’Hare Marble Shop and the Joseph Foster Stone Yard. In February of 1880 he left Cincinnati for Chillicothe, Ohio, then on to Boston in search of work. He returned to Cincinnati in 1882 and went to work at the Rookwood Pottery Company. Again this was a short lived job and he left Rookwood to go into business with Matt Morgan, as a modeler at the Matt Morgan Art Pottery Company in Caseyville, Ohio. Orlando worked with Mogan for almost a year before moving on to the American Encaustic Tile Works in Zanesville, Ohio. He left there after 4 months, heading back to Cincinnati, where he spent a month working for the Kensington Tile Company before leaving Cincinnati for Chicago. In February of 1885 Giannini moved to Chicago, Illinois to become a foreman and designer at the Adams and Westlake Company, a brass and bronze foundry that supplied metal workings primarily for the railroad industry. He seemed to be happy in Chicago as he reported back to the XntricX, the spelling changed in 1879, that for a designer he “must say Chicago is for my line of work far ahead of any place I’ve been.”

Through his associations with others in his field, he became acquainted with Frank Lloyd Wright. On his first visit to Wrights' house in Oak Park, Illinois, he suggested to Wright that he would paint a mural on the large semi-circular wall of his second story playroom. He immediately began to sketch the outline of "The Fisherman and the Genie" mural, based on a tale from the Arabian Nights. He worked on the painting for many following Sundays until its' completion. After completing the playroom mural, Wright had him paint two more murals on his bedroom walls, both depicting American Plains Indians. In 1895 Giannini painted his last mural for Wright in his commission for the Chauncey L. Williams house in River Forest, Illinois.

In 1899 Giannini partnered with Fritz Hilgart, and the firm of Giannini and Hilgart began designing art glass windows. The partners executed designs for numerous Prairie School and Chicago architectural firms. Besides designing art glass windows, Giannini and Hilgart also produced Teco glass lamp shades for Gates Pottery, the creator of Teco pottery. That style of  lamps were popular at the turn of the century.

Giannini is attributed with introducing Wright to his former employer at Westlake and Adams, Ward Willits, for whom Wright designed his seminal prairie house in Highland Park, Illinois in 1902. He is also responsible for providing many fireplace tile mosaics for houses designed by noted architect George W. Maher.

By 1907 Giannini had left the partnership and moved La Jolla, California where he continued working until his death in 1928. The firm of Giannini and Hilgart still exists, in the glass design business in Chicago, Illinois.