[1] He then entered the Sulpician-run seminary of Montferrand in 1831, and upon completing his course in philosophy and theology, was ordained to the priesthood by Bishop Louis-Charles Féron on December 17, 1836.

[2] He served as a curate in Le Cendre until 1839, when he accepted the invitation of Bishop John Baptist Purcell to join the Diocese of Cincinnati, Ohio, in the United States.

He served as pastor at Albuquerque (1853–1858) and at Santa Fe (1858–1860) before being transferred to Colorado, where he was thrown from his carriage while descending a spur of the Rocky Mountains and left lame.

On March 3, 1868, Machebeuf was appointed Vicar Apostolic of Colorado and Utah as well as Titular Bishop of Epiphania in Cilicia by Pope Pius IX.

[2] He founded an academy and a school for boys in Denver (not to be confused with the college preparatory high school named in his honor, but founded after his death), a convent of the Sisters of Loretto, St. Joseph's Hospital, House of the Good Shepherd and the College of the Sacred Heart (now part of Regis University).