Nathaniel Collins McLean was born to Supreme Court Justice John McLean and his wife, Rebecca (Edwards) McLean, in Warren County, Ohio on February 2, 1815. He earned his BA from Augusta College (Kentucky) in 1834 and his LLB from Harvard Law School in 1838. In that year, he married Caroline Thew Burnet, daughter of Judge Jacob Burnet, and moved to Cincinnati, Ohio to practice law. Caroline McLean died on April 12, 1856, and Nathaniel McLean married Mary Louise Thompson in 1858. He had a total of 13 children, six by his first wife and seven by his second: Rebecca Burnet (1839-1851), Jacob Burnet (1841-1926), Caroline Burnet (1843-), Nathaniel Collins (1845-1846), Evelyn Elizabeth (1851-), John (1854-), Nathaniel Collins (1861-1861), Elizabeth Maud (1862-), Larz Anderson (1864-1876), Mary Louise (1865-), Nathalie (1867-), Marshall (1869-), and Henriette Post (1872-).

At the beginning of the Civil War, McLean organized the 75th Ohio Volunteer Infantry under the authority of Major General John C. Freemont. He was appointed Brigadier General of Volunteers in 1862 and commanded the 2nd Brigade of the 1st Division (XI Corps) at Chancellorsville. He became the commander of the Division when General Charles Devens was wounded. McLean went on to serve as the Provost Marshal of the Department of the Ohio and then commanded in Kentucky and led the 1st Division (XXIII Corps) in the Atlanta Campaign. Finally, McLean commanded the 3rd Brigade of the 2nd Division (XXIII Corps) in the Carolinas Campaign before resigning in April of 1865.

After leaving the Army, McLean returned to his family in Ohio. He soon moved to Frontenac, Minnesota where he farmed and raised sheep. In 1885, he moved to Bellport, Long Island, where he lived in comparative retirement until he died on January 5, 1905.