Wesley River booked his first audition at four years old. It was a recurring role on HBO's The Pitt.

He plays Tyler Jones, a young boy brought to a hospital after accidentally ingesting a cannabis gummy. The role spans two episodes in Season 1. The Pitt premiered January 9, 2025 and is produced by R. Scott Gemmill, John Wells, and Noah Wyle.

In September 2025, Deadline reported that River had been cast as the lead in Foster, a 1980s-set action thriller directed by Emmy winner Timothy Woodward Jr. He was five years old. The film stars James Franco, Ron Perlman, Natalie Burn, Dash Mihok, Alexis Knapp, James Frain, and Jeremy Luke. River plays Charlie, a young boy left on the doorstep of a man fighting to stay sober. Born To Burn Films is producing. Top Film Distribution introduced the project to buyers at TIFF 2025. Delivery is planned for 2026.

River is from Los Angeles. He is six years old. His first credit was a recurring role on an HBO drama. His second is a feature film lead. He is repped by Abby Johnson at Thruline Entertainment and Danny Bjelajac at Love Talent Agency.