Upjohn, the son of famous architect Richard Michell Upjohn, was born in New York City. He earned a degree in mechanical engineering from the Stevens Institute of Technology in Hoboken, New Jersey, in 1899. After holding several jobs, including assistant principal of the School of Architecture of the International Correspondence Schools in Scranton, Pennsylvania, he started working for his father’s architectural firm in 1903. Soon after, Upjohn opened his own practice in 1905 in New York, entering into a brief partnership with George Conable from 1908 to 1914.
Like his father, Upjohn primarily designed churches, but he also worked on academic and private residential commissions. In North Carolina, he designed nearly 50 churches and educational buildings, including more than 40 during the 1920s alone. Completed in 1914, his first major commission in North Carolina was to design the parish house and chapel of Christ Church along Capitol Square in Raleigh, the main building of which had been designed by his grandfather. Upjohn's plan formed a partly enclosed garden on the north side of the original church. In 1919 he worked on the North Carolina State University campus master plan in collaboration with landscape architect Warren Manning, designing Brooks Hall and the Chancellor’s Residence. Upjohn was named a Fellow of the American Institute of Architects (FAIA) in 1930 and closed his practice in 1945. He died at the age of 73.