Nelson was born in Montréal, the son of William Nelson, a teacher, and Jane Dies, daughter of an important land owner in the New York area. He studied medicine in Montreal and later at Harvard in the state of Massachusetts. He began practicing medicine in April 1814. During the second American invasion, he was surgeon for the Deschambault Corp and the Indian Braves Corp.
In 1827, he entered politics at the invitation of his brother, Wolfred Nelson, also a doctor and member of the Parti Patriote. He became a important voice of the Patriotes movement later.
On November 24, 1837, he was arrested with other politicians. He was freed soon after, not being involved with the rebels, unlike his brother Wolfred who participated in the Battle of St-Denis. His arrest will however lead him to join with the Patriotes exiled in the United States.
The leaders of the Patriotes voted for the quick establishment a provisional government and the launch an attack from the United States. Some important Patriotes voted against this idea, including Louis-Joseph Papineau, leader at the time. Robert Nelson was made General of the army and elected future President of the Republic of Lower Canada.
On February 28, 1838, Nelson passed to Lower Canada at Alburg in the State of Vermont with some 300 men. He proclaimed the independence of Lower Canada and distributed copies of a declaration of independence. Soon after, they were arrested by the American army for violation of the law of neutrality of the United States. Robert Nelson was arrested. A jury sympathetic to the Patriotes cause liberated him and others.
After this failed attempt, Robert Nelson and other Patriotes decided to take the time to organize a new strike. A second invasion started on November 3, 1838. Things didn't go as planned and the rebels were forced to retreat.