Stephen Sewell qualified for the New Brunswick bar after training with Ward Chipman, then moved to Montreal and established a legal practice in 1791. Merchants and seigneurs became important clients, and by the early nineteenth century he had a prosperous practice. His land purchases and commercial investments proved less successful. He also joined the local militia, becoming a captain in 1812, and strongly supported the colony's British governing party.

Appointed solicitor general of Lower Canada in 1809, Sewell entered the assembly for Huntingdon that year and represented Montreal East after the 1810 election. His hostility to Governor George Prevost's conciliatory administration contributed to his downfall. After his authorship of a critical Montreal Herald article became known, he was suspended and dismissed from the solicitor generalship in 1816. Efforts to regain that office or secure a judgeship failed, despite his brother Jonathan's influence.

Sewell continued legal and institutional work. In 1817 he kept a journal as secretary to boundary commissioner John Ogilvy, later served as a Lachine Canal commissioner, and negotiated the transfer of James McGill's Burnside property for the future college. He helped found Montreal's Natural History Society in 1827 and the lawyers' library in 1828, serving as president of both. Named king's counsel in 1827, he remained active until cholera killed him in 1832. His debts left his widow and children an insolvent estate.