She became a member of the Alaska Bar Association in 1987. She was an attorney in Anchorage, Alaska from 1985 to 1998. She also served, from 1990 to 1991, on the mayor's task force on the homeless.
In 1998, she was elected to the Alaska House of Representatives and served as House Majority Leader for the 2003–2004 session. Murkowski sat on the Alaska Commission on Post Secondary Education and chaired both the Labor and Commerce and the Military and Veterans Affairs Committees. In 1999 she introduced legislation establishing a Joint Armed Services Committee.
Murkowski is married to Verne Martell. She has two children, Nic and Matt. Her father, Frank Murkowski, was Governor of Alaska from 2002 to 2006 in addition to being her immediate predecessor in the Senate.
Murkowski, while a member of the state House, was appointed by her father, Governor Frank Murkowski, to his own unexpired senate seat in December 2002, which he had vacated after being elected governor. She was subsequently elected to a full six-year term against former Governor Tony Knowles in the 2004 election, after winning a primary challenge by a large margin. Near the end of the general campaign, senior senator Ted Stevens shot campaign ads for Murkowski and warned the public that if a Democrat replaced Murkowski they were likely to receive fewer federal dollars.
Murkowski is a member of the Republican Main Street Partnership and supports stem cell research. She is also a member of the Republican Majority For Choice, Republicans For Choice, and The Wish List (Women in the Senate and House), a group of pro-choice women Republicans.
In July 2007, Murkowski stated she would sell back land she bought from Anchorage businessman Bob Penney, a day after a Washington watchdog group filed a Senate ethics complaint against her, alleging that Penney sold the property well below market value. The Anchorage Daily News noted, "The transaction amounted to an illegal gift worth between $70,000 and $170,000, depending on how the property was valued, according to the complaint by the National Legal and Policy Center. According to the Associated Press, Murkowski bought the land from two developers tied to the Ted Stevens probe.
In 2008, Murkowski amended her Senate financial disclosures for 2004 through 2006, adding income of $60,000 per year from the sale of a property in 2003, and more than $40,000 a year from the sale of her "Alaska Pasta Company" in 2005.
Murkowski voted with Democrats and moderate Republicans on H.R. 976, which called for the expansion of the State Children's Health Insurance Program (SCHIP) to provide coverage for additional uninsured children. That bill passed both the House and the Senate, but was vetoed by President Bush. She supports health care reforms in her native state as well, largely because health care costs for Alaskans are up to 70% higher than costs in the continental United States.
On abortion, Murkowski has a "mixed record" rating (50%) from the National Right to Life Committee, and a pro-life rating (14%) from the National Abortion Rights Action League (NARAL).
On voting rights, Murkowski supported the Republican leadership's continued denial of representation in the Congress for DC, voting against bringing the DC Voting Rights Act to the floor.
On environmental issues, for 2003, the nonpartisan watchdog group League of Conservation Voters rated Murkowski at 11% on environmental issues: "During her short time in the Senate," Murkowski, who chairs the Senate Energy and Natural Resources Subcommittee on Water and Power, "has thrown her support behind efforts to drill for oil in the Arctic National Wildlife Refuge (ANWR). For the 109th Congress, Republicans for Environmental Protection, a conservative group dedicated to environmental causes, issued Murkowski a rating of 2%, noting that in 2006 she voted:
Most Democrats and some moderate Republicans oppose Arctic oil drilling because of concerns about environmental damage. Murkowski believes that recent technological developments make it possible to drill without incurring such damage.
On December 14, 2007, the Senate passed an energy bill that, among other things, encourages the use of renewable fuels. The legislation, which Murkowski supported, raises the renewable fuels standard to require the production of 36 billion gallons of biofuels by 2022, compared to the current production of about 7 billion gallons a year.