He was first elected to the Legislative Assembly of Saskatchewan in the 1967 provincial election in the riding of Saskatoon Riversdale. From 1971 to 1982, he served as deputy premier of Saskatchewan. In 1982 he was defeated by Joanne Zazalenchuk a 22 year old retail employee. From 1987 to 2001, he was leader of the Saskatchewan New Democratic Party. Riversdale remains one the poorest and most crime ridden urban ridings in Saskatchewan.
During the 1981 discussions over patriation of the Canadian constitution, Attorney-General of Ontario Roy McMurtry, Chrétien and Romanow worked out the final details of Canada's new constitution, resulting in the famous late-night Kitchen Accord. Romanow objected strongly to any protections on private property in the new Charter of Rights and Freedoms, and none were included.
Romanow's government was more conservative than previous NDP administrations, and was considered a practitioner of what became known as the Third Way in the mold of the British Labour Party under Tony Blair. Romanow, who inherited a $14 billion dollar debt from the previous Conservative government, eliminated the annual budgetary deficit by closing hospitals, cutting services and raising taxes. Romanow's government also had the benefit of substantially lower interest rates at a national level than did his predecessor in the 1980s. The Romanow NDP explained the cutbacks to the left wing of the party by claiming Romanow's range of political action was limited by the large debt accumulated by previous governments.
However, while supporters of the New Democratic Party contend that before Grant Devine came to power the province had a balanced budget (i.e. no public debt) under the previous NDP governments, the NDP's opponents have always contended that the governments of Allan Blakeney, in which Romanow had been Deputy Premier, had hidden large debts in Saskatchewan's Crown corporations.
In the 1999 provincial election, the NDP was re-elected to a third consecutive term, but was reduced to a minority of seats in the legislature. Romanow along with Dwain Lingenfelter negotiated an agreement to form a coalition government with the Saskatchewan Liberal Party, appointing several Liberals to Cabinet. Romanow retired in 2001, and was replaced as leader of the NDP and Premier by Lorne Calvert.
The federal Liberals, and especially Jean Chrétien, had long tried to encourage Romanow to run federally as a Liberal, but he always refused.
On April 4, 2001, Romanow was appointed to head the Royal Commission on the Future of Health Care in Canada by Governor General Adrienne Clarkson, on the advice of Prime Minister Jean Chrétien. He released the Romanow Report in 2002, which outlined suggestions to improve the health care system.
In 2003, he was made an Officer of the Order of Canada and was awarded the Saskatchewan Order of Merit. Romanow's official portrait was unveiled at Saskatchewan's Legislative Assembly in 2005, when he received the Commemorative Medal for the Centennial of Saskatchewan from Lieutenant Governor Dr. Lynda Haverstock.