Born in Burley, Simpson was raised in Blackfoot, where his father was a dentist. He graduated from Blackfoot High School in 1968, Utah State University in Logan in 1972, and the Washington University School of Dental Medicine in St. Louis, Missouri, in 1977. Simpson practiced dentistry in Blackfoot until his election to Congress in 1998. He was elected to the Blackfoot City Council in 1980 and was elected to the state legislature in 1984, the first of seven terms. He was the Speaker of the Idaho House prior to his election to Congress.
Simpson entered the 1998 campaign for the U.S. House seat vacated by Mike Crapo, who was running for United States Senate. He defeated former Democratic Congressman Richard H. Stallings in the general election. Simpson did not face serious opposition in 2002 and 2004. In 2006 Simpson defeated former Democratic state representative Jim D. Hansen, son of former Republican Congressman Orval H. Hansen, to win reelection.
During the 2007 scandal involving Senator Larry Craig (R-ID), Simpson was openly considered for an appointment to the U.S. Senate in the event that Senator Craig resigned. Simpson, however, asked Governor C.L. "Butch" Otter to remove his name from consideration, claiming that the Idaho Congressional Delegation would be in a better position if he were to remain in the House and retain his seniority on the House Appropriations Committee.
During the 2008 Presidential primaries, Simpson was an early supporter of former Massachusetts Governor Mitt Romney and a member of his Congressional Whip Team.
Following the death of Congressman Charlie Norwood (R-GA) in February, 2007, Simpson has become a leading advocate of the American Dental Association (ADA) in Congress, in part because his profession is dentistry. The advocacy inspired Simpson to introduce legislation regarding methamphetamine, specifically how the drug affects tooth decay or "methmouth". The bill is formally called H.R. 1671: Meth Mouth Prevention and Community Recovery Act, with the purpose to understand and address the oral health problems associated with methamphetamine. The bill's goals are to expand and intensify the Department of Health and Human Services, make grants available to educate 12- to 17-year-olds about methmouth, and to promote a series of education activities for all dentists to learn about substance use disorders and their relationship to oral health and the provision of dental care. As of March 24, 2009, the bill was put from the House Committee on Energy and Commerce to the Subcommittee on Health where it has been debated, but never brought to a conclusion. As soon as that happens, it will be brought up before the whole committee, then later the House of Representatives.
Simpson is a strong supporter of the domestic sugar beet producers, and the Idaho potato growers. In 2010, Simpson took up the cause, alongside his former Democratic colleague, Walt Minnick, the lead sponsor of the bill, to secure a third federal judge for Idaho. Simpson was quoted as saying, "The caseload of the Idaho District Court has increased significantly in recent decades resulting in Idaho’s district judges carrying a disproportionate share of cases in relation to their colleagues in other states."
Simpson is a member of the Republican Party. However, he is known to be pragmatic on certain issues. For Example, he was one of a handful of Republicans to vote in favor of the reauthorization of the State Children's Health Insurance Program (SCHIP) in the 110th Congress. He has also been a supporter of the National Endowment for the Arts and the National Endowment for the Humanities, voting each year against Republican amendments to strip them of funding. In the past, he has opposed "earmarks", or congressionally directed spending.
Simpson was an original co-sponsor of the Newborn Screening Saves Lives Reauthorization Act of 2013 (H.R. 1281; 113th Congress), a bill that would amend the Public Health Service Act to reauthorize grant programs and other initiatives to promote expanded screening of newborns and children for heritable disorders. Simpson said that "the bill reflects the realities of reduced budgets Washington, but continues and strengthens the well established system of monitoring and evaluating infant conditions soon after birth. Just one small blood sample from the newborn’s foot identifies infants with genetic or other conditions that can be treated quickly and effectively, saving and improving thousands of lives."
On March 21, 2014, Simpson introduced the bill To amend the Wild and Scenic Rivers Act to authorize the Secretary of the Interior to maintain or replace certain facilities and structures for commercial recreation services at Smith Gulch in Idaho (H.R. 4283; 113th Congress). The bill would require the United States Secretary of Agriculture to permit private entities to repair or replace certain commercial facilities on United States Forest Service land in Idaho. Simpson said that "this legislation clarifies Congress' intent of the 2004 amendments to the Wild and Scenic Rivers Act which continued the existing use and occupancy of commercial services in this corridor of the Salmon River".
Simpson's hallmark legislation in the House of Representatives has been the Central Idaho Economic Development and Recreation Act (CIEDRA), which would create 312,000 acres of wilderness in central Idaho, much of which is currently a wilderness study area. Simpson has faced substantial resistance from groups like the Sierra Club who claim the bill lacks "wilderness values" because the bill allows for motorized access to certain portions of the wilderness area and some federal land would be transferred to the State of Idaho to promote the economic development of the local community and the recreational use of National Forest land and other public lands in central Idaho. Simpson has also faced opposition from groups who oppose new federal land designations, and wilderness designations particularly because of restricted access to wilderness areas. In August 2015 a revised version of CIEDRA, the Sawtooth National Recreation Area and Jerry Peak Wilderness Additions Act, passed Congress and was signed by President Obama, creating the Hemingway–Boulders, Jim McClure–Jerry Peak, and White Clouds wilderness areas, which cover a total of 275,665 acres (111,558 ha) of central Idaho.
Simpson voted in favor of the Tax Cuts and Jobs Act of 2017. After passing the bill, Simpson said he spoke to Idaho farmers, ranchers and businesses who called for a simplified tax code and reform. He says the bill will "create economic growth in the United States by unleashing American small businesses and unburdening middle class families so they can make better financial decisions with their own money.”
Simpson rankled Senate leadership during the Craig scandal by criticizing them for their treatment of the Senator. Simpson is quoted as saying, "If that’s how they treat their own, that tells me they’re more interested in party than individuals, and the party is made up of individuals. How you treat them says a lot about your party." Simpson is not known to have condoned Craig's alleged misconduct, but he demanded that Craig be treated fairly. For Example, he is quoted as saying, "They have people over there [in the Senate Republican Conference] in far worse trouble that they haven’t said a thing about."