McGuire was selected to stand for election for Labour through an all-women shortlist. She was elected to the House of Commons at the 1997 general election when she ousted the then Secretary of State for Scotland Michael Forsyth by 6,411 votes. In the same year as her first election, she was rewarded by becoming the Parliamentary Private Secretary to Secretary of State for Scotland Donald Dewar. A year later, she joined the New Labour government when she was appointed as an assistant whip, becoming a Lord Commissioner to the Treasury in 2001. She became a Parliamentary Under-Secretary of State for Scotland in 2002, moving sideways to the Department for Constitutional Affairs in 2003. She served in the Department for Work and Pensions with responsibility for disabilities from 2005 to 2008. In October 2008, she stood down from the government and it was announced she would be appointed to the Privy Council.