Della Bosca attended school at De La Salle College in Cronulla. Influenced by a visit to his school by Bob Carr, Della Bosca joined the ALP in January 1973. He rose through his branch and electorate council to take a place on the party's National Executive. Between 1976 and his election to parliament in 1999, Della Bosca worked for the labour movement full-time in various capacities, first as a researcher for Senator Kerry Sibraa. In 1979, he took on the role of National Research Officer for the Australian Transport Officers' Federation, becoming the union's state organiser in 1981.
In 1983, Della Bosca became State Organiser for the ALP. In 1985, he was promoted to Assistant Secretary and in 1990 he attained the position of general secretary, a post he was to hold for nine years.
In 1999, Della Bosca made his much-anticipated move into parliamentary politics as a candidate for the Legislative Council. Within a month of his election, Premier Bob Carr appointed him Special Minister of State. In 2000, he was set to become the ALP's next national president, but was forced to withdraw after he criticised then ALP leader Kim Beazley's GST rollback policy in an interview in the news magazine, The Bulletin.
Della Bosca's ministerial responsibilities were expanded following the 2003 election to include Commerce, Finance, Industrial Relations, Ageing and Disability Services. He was also appointed Leader of the Government in the Legislative Council. Following the 2007 election he was appointed Minister for Education and Training, Minister for Industrial Relations and Minister for the Central Coast. On 4 September 2007 Della Bosca stated "the NSW government strives to keep (TAFE) fees as low as possible". Despite this, he announced that course fees would be increasing by 6.5 per cent to 9 per cent.
In May 2008, Della Bosca revealed his probationary driver's licence had been revoked for a period of six months following multiple speeding offences. At the time of the ban Della Bosca was in charge of the Motor Accidents Authority. Later that month, he caused further controversy by swearing at a media photographer who photographed him cycling to work.