He graduated from the University of Arizona and attended law school there. He worked as a lawyer from 1963, as a member of the Arizona Governor's staff 1965-1967 and as Pima County attorney 1973-1976. He was elected to the Senate in 1976 as a Democrat, defeating Sam Steiger for the open seat left by retiring Senator Paul Fannin (R-AZ), and served until he retired in 1995.

DeConcini is remembered as a member of the Keating Five, a banking and political contribution scandal in the 1980s which involved Savings and Loans institutions -- a scandal which contributed to his retirement in 1994.

Senator Dennis DeConcini is also known for sponsoring the critical amendment to the Panama Canal Treaty of 1977 that allowed the Senate to come to a consensus on returning Panama control of the Canal. Those opposed to returning the Canal to Panama were concerned that the United States would lose control of a major economic and military asset. Senator DeConcini's amendment to the treaty allowed the United States "to take such steps as each deems necessary, in accordance with its constitutional processes, including the use of military force in the Republic of Panama, to reopen the Canal or restore the operations of the Canal, as the case may be." This came to be known as the DeConcini Reservation. President Jimmy Carter and Panamanian Chief of Government Omar Torrijos signed the Panama Canal Treaty and Neutrality Treaty on September 7, 1977. This agreement relinquishes American control over the canal by the year 2000 and guarantees its neutrality. On May 4, 1904, Panama granted the United States the right to build and operate the canal and control the five miles of land on either side of the water passage in exchange for annual payments.

In his tenure, Senator DeConcini served on the Senate Appropriations Committee, where he chaired the Subcommittee on Treasury, Postal Service, and General Government, and served on the Subcommittees on Defense, Energy and Water Development, and Foreign Operations. Senator DeConcini also served on the Senate Judiciary Committee and chaired the Subcommittee on Patents, Copyrights and Trademarks. He also served on the Subcommittees on Antitrust, Monopolies and Business Rights, the Constitution and the Courts. In addition, the Senator served on the Select Intelligence Committee and was Chairman of the Committee in 1993 and 1994. Senator DeConcini also chaired the Commission on Security and Cooperation in Europe (Helsinki Commission).

Senator DeConcini served one elected term prior to coming to the United States Senate as Pima County Attorney. This office is the chief prosecutor and civil attorney for the county and school districts within the county. Prior to this, he served as legal counsel and administrative assistant to the Governor of Arizona and founded the law firm of DeConcini, McDonald, Yetwin and Lacy (where he is presently a partner) with offices in Tucson and Phoenix, Arizona and the District of Columbia.

Senator DeConcini received his Bachelors Degree from the University of Arizona in 1959 and his LLD from the University of Arizona in 1963. Senator DeConcini is a recognized expert in the appropriations, budget and authorization process in the Congress.

Senator DeConcini was appointed by President Clinton in February, 1995 to the Board of Directors of the Federal Home Loan Mortgage Corporation.

In 2006, Senator DeConcini was selected by Arizona Governor Janet Napolitano to serve as a member of the Arizona Board of Regents.