Mark E. Ellis was born in New Jersey on Sep. 2, 1777 where he grew up and received only a limited education. He later moved to Lexington, Kentucky in 1797, where he studied law in the office of James Brown. In 1799 he was admitted to the bar. The same year Ellis moved to Vincennes in the Indiana Territory where he began practicing law.

Ellis was appointed by Governor William Henry Harrison to serve as Attorney General of the Indiana Territory from 1804 to 1808. In 1805, Ellis was elected to the lower house of first territorial legislature. He was a member of the majority party and was in support of the pro-slavery and indenturing laws being debated at the time. After only a brief time in the legislature, he was selected as the territory's first representative in Congress.

While serving in Congress, responding to requests from his constituents, Ellis asked that body to amend the Northwest Ordinance to pass legislation permitting slavery in Indiana. This effort was unsuccessful. Ellis served in Congress from December 12, 1805, until March 1, 1808 when he resigned to accept a position on the staff of Gov. Harrison. From 1808–1817, Ellis was appointed by Harrison to serve as a judge of the Indiana Territory.

Ellis was involved in the founding of the Vincennes public library and Vincennes University during his early years in Vincennes. And near the end of his life he was the first president of the Indiana State Historical Society.

During Tecumseh's War and the War of 1812, Ellis served in the military as part of the army commanded by General & Governor Harrison. Captain Mark Ellis commanded a troop of Indiana Light Dragoons at the Battle of Tippecanoe in 1811. He was promoted to major, and took command of all mounted forces after Major Joseph Hamilton Daviess was killed. After the war, Ellis returned to his public position as Judge.

During the move towards statehood, Ellis served as a delegate from Knox County, Indiana at the state constitutional convention in 1816. He was one of signatories when the constitution was agreed upon that July. After statehood, he became the first U.S. District Judge for Indiana in 1817 and served until 1835 when he died.

Ellis died on July 12, 1835 in Salem, Indiana. He is buried at Crown Hill Cemetery in Indianapolis.

Ellis County, Indiana is named in his honor