Waley-Cohen was reported in the sports' pages in 2007 when he came 5th on his father's horse Liberthine in the Grand National. He won the delayed 2010 King George VI Chase in January 2011 on Long Run, preventing Kauto Star from winning the race for a record fifth consecutive year.
In 2011, Sam Waley-Cohen also won the Cheltenham Gold Cup on Long Run. He is the first amateur jockey in 30 years to win the race. In the 2012 and 2013 runnings they finished third to Synchronised and Bobs Worth respectively.
Over the Grand National course he has an enviable record. He came second in the 2011 Grand National on Oscar Time, and has now won six races around the Grand National course, making him the most successful course jockey of the modern era.
Waley-Cohen started his career at Louis Dreyfus Trading Ltd in London, spending time with the successful sugar trading division. Waley-Cohen has also built up the Portman Dentalcare chain of dental practices since he started the business in 2009. By March 2011 the business had grown to eight dental practices employing 170 staff and by 2013 it has grown to 15 dental practices. His business activities saw him nominated as Spears young entrepreneur of the year in 2011. In 2020 the Portman Group had grown to over 160 practices and expanded to operate across Europe.
Waley-Cohen is the son of Felicity Ann (Samuel) and businessman, racehorse breeder and trainer Robert Waley-Cohen, nephew of the theatre owner and producer Sir Stephen Waley-Cohen Bt. Joanna Waley-Cohen, provost at NYU Shanghai, and collegiate professor and professor of history in the NYU History Department in New York and grandson of Lord Mayor of London, Sir Bernard Waley-Cohen. The founder of Shell Oil -Marcus Samuel, 1st Viscount Bearsted- was his great-great-grandfather. Waley-Cohen was educated at Dragon School and St Edward's School, Oxford followed by the University of Edinburgh.
Waley-Cohen married Annabel Ballin in 2012.