Richard entered his father's office at the age of eighteen. After serving as draftsman until 1851 he joined the elder architect in partnership under the firm name of Upjohn & Company, and was closely associated with his father on practically all of the firm's major works, particularly in the period between 1860 and 1876. Among the churches with which he was identified was the Madison Square Presbyterian in New York; Trinity Church, Princeton, N. J., Grace Church in Newark, N. J„ St. Peter's in Geneva, N. Y„ and the Central Congregation in Boston. In addition he completed St. Mark’s Pro Cathedral in San Antonio, Texas, the cornerstone of which was laid in 1859, but construction was delayed during the Civil War.
Following his father’s decease (1878) Mr. Upjohn practiced independently in New York, and although his work was not pre-eminently ecclesiastical he designed a number of churches of note, St. Paul’s Cathedral, Fond du Lac, Wis., Grace Episcopal at Anniston, Ala.; DeLancey Memorial Church, Geneva, N. Y., Presbyterian Church and Manse, Rye, N. Y., and the American Church of St. John in Dresden, Germany, considered one of this architect's outstanding achievements in ecclesiastical design. Mr. Upjohn however was more widely known as the architect of the Connecticut State Capitol at Hartford, completed in 1885 from drawings prepared early in his career.
After 1890 he practiced only during brief periods, and five years later retired to his home in Brooklyn, where his death later occurred. His son, Hobart Brown Upjohn was a member of the third generation of the family to choose a career in the field of Architecture.