Macalester was born in Philadelphia on February 17, 1798; his father was a shipping merchant. As a teenager, he led a company of forty boys who constructed a fort on the Schuylkill during the War of 1812. He graduated from the University of Pennsylvania. From 1821 to 1827, he worked as a merchant in Cincinnati, Ohio, before returning to Philadelphia. On Aug. 24, 1832, his father died, leaving Macalester a large estate. Macalester retired as a merchant in 1849, but continued buying and selling securities and real estate.
In the 1870s, Rev. Dr. Edward Duffield Neill turned to Macalester for sponsorship for the failing institution in Minnesota known as Jesus College. Macalester donated a building near Saint Anthony Falls, and the college was chartered in 1874. The college moved to its present location, on Snelling Avenue at Grand Avenue in St. Paul, in 1885 after building an endowment and seeking the help of the Presbyterian Church. Macalester also served as president of the Orthopedic Hospital and the St. Andrew's Society.
Macalester had one son and one daughter. He died at his home in Philadelphia on December 9, 1873. In his will, he bequeathed $5,000 for Presbyterian missions, $5,000 for the Presbyterian Board of Education, and $5,000 for the Fund for Disabled Ministers of the Presbyterian church. He also left a large property to Macalester College, and other charitable bequests.
- Kilde,Jeanne Halgreen. Nature and Revelation: A History of Macalester College. University of Minnesota Press, 2010, p. 62
- Kilde, Jeanne Halgreen. Nature and Revelation: A History of Macalester College. University of Minnesota Press, 2010, p. 81
- America's Successful Men of Affairs: The United States at Large, Henry Hall, 1896, p. 538