Henderson began his professional career in England in 2001 with super league side Salford City Reds. With limited opportunities there, Henderson moved to Northern Ford Premiership club Barrow Raiders for the 2002 and 2003 seasons. He captained the Raiders for the 2003 season. Soon after, Super League side Widnes Vikings snapped up Henderson for a trial period, in which he featured for them in the 2004 Sydney World Sevens tournament, and a friendly match against the Wests Tigers. He failed to agree a deal with Widnes and subsequently joined the Wests Tigers, captaining their premier league side Balmain Tigers in 2004. Henderson joined Castleford Tigers for the 2005 season after their relegation from the Super League. He spent 4 seasonsat the club. Henderson captained the side twice to promotion to the Super League in 2005 and 2007. The 2008 Super League season was to be his final year at Castleford after the club and Henderson failed to agree terms on a new deal. Henderson wanted to stay and made it clear to the fans in the final game of the season. The Castleford fans also wanted Henderson to stay and in the final home game the fans sung his name and chanted 'Sign him on!' Also during 2008, Henderson, along with brother Kevin, made head lines when they were set to take the Rugby Football League to court over rules changes to the current quota system, which they felt would affect their super league careers. He signed for Championship side Gateshead Thunder for the 2009 season in the Championship. Henderson spent only one season with Gateshead as the club were faced with financial problems and a shareholders dispute leading them into administration. This forced Henderson to look elsewhere and he joined Championship winners Barrow Raiders in the 2009 close season on a two-year deal. Henderson left Barrow and joined Sheffield Eagles towards the end of the 2010 season, after the Barrow club failed to honour his contract. Henderson went on to play just over four successful seasons with Sheffield, with 2014 being his final year. In his time here he was enjoyed a grand final appearance in 2011 and back to back grand final victories in 2012, and 2013. The Hendersons are a Scottish family and all three brothers play for Scotland at international level. Henderson began his international career in 2003 featuring in the European Nations Cup. He went on to make 17 test appearances in European competitions and 5 World Cup appearances in 2008 and 2013 finishing his international career in Scotland's World Cup quarter final match against New Zealand in Leeds. All three brothers featured in the Scotland squad for the 2008 Rugby League World Cup.
On 11 July 2014, London Broncos head coach Joe Grima appointed Andrew Henderson as his assistant beginning in November. On 2 March 2015, Joey Grima resigned after ten months in charge and just 3 games into the Championship season. Henderson took charge of the Championship side on an interim basis. After 2 games in charge with 1 win and 1 loss, he was appointed as the Broncos new permanent head coach. Andrew Henderson led the Broncos to an average 7th-placed finish in the 2015 Championship and 3rd place in the Championship Shield, eventually losing the Shield Final to Featherstone Rovers 34–6 at the Select Security Stadium in Widnes. In 2016 he guided the Broncos to a 2nd-place finish in the Championship taking them into the Super 8's Qualifiers for the chance to gain promotion. The Broncos finished a reasonable 6th place on points difference with wins over Batley, Salford and Featherstone. They just missed out on the million pound game to Salford. In 2017, they currently sit joint 2nd in the Championship. The Broncos are the only team to have won on all 3 occasions under the guidance of Henderson at the Summer Bash event. They have recorded a 42-6 win and 32-14 win over Sheffield Eagles in 2015 and 2016. In 2017 they defeated Featherstone Rovers 42-16.
