In 1921 Henderson moved to Aberdare Athletic. He only played 19 games for his new club before he was signed by Syd King, the manager of West Ham United for a fee of £650. Henderson joined a team that included Syd Puddefoot, Jimmy Ruffell, George Kay, Edward Hufton, Richard Leafe, Jack Tresadern, Vic Watson, Sid Bishop, Billy Brown and Jack Young.
Henderson soon established himself as the first-team right-back. Coincidently, his left-back partner, Jack Young, was also born in Whitburn. West Ham enjoyed a good FA Cup run in the 1922-23 season beating Hull City (3-2), Brighton & Hove Albion (1-0), Plymouth Argyle (2-0), Southampton (1-0) and Derby County (5-2) to reach the final against Bolton Wanderers. The final took place at Wembley Stadium, only four days after the stadium had been completed.
The stadium had a capacity of 125,000 and so the Football Association did not consider making it an all-ticket match. After all, both teams only had an average attendance of around 20,000 for league games. However, it was rare for a club from London to make the final of the FA Cup and supporters of other clubs in the city saw it as a North v South game. It is estimated that 300,000 people attempted to get into the ground. Over a thousand people were injured getting in and out of the stadium. When the game eventually got started, Joe Smith and David Jack scored in Bolton's 2-0 victory over West Ham United.
In their next game West Ham United beat Sheffield Wednesday 2-0 to ensure promotion to the First Division. Vic Watson was top scorer with 22 goals and Billy Moore added 15 more. Henderson played in 43 league and cup games that season.
West Ham United finished in 13th place in their first season in the First Division. Henderson only missed one league game in the the 1923-24 and 1924-25 seasons and there was talk of him being selected for England. However, a serious knee injury in 1925 forced him out of the team for 18 months. When he returned in the 1927-28 season he was unable to recapture his earlier form and was forced into retirement.
Billy Henderson died of tuberculosis in 1934.