| Name | First Elected | Departure details | Replaced by |
| Senate | | | |
| Paul G. Kirk Jr., D-Mass. | 2009 | Resigned from office effective Feb. 4, 2010 | Scott P. Brown, R-Mass. - Elected Jan. 19, 2010 |
| Mel Martinez, R-Fla. | 2004 | Resigned from office effective Sept. 9, 2009 | George LeMieux, R-Fla. - Appointed Sept. 10, 2009 |
| Edward M. Kennedy, D-Mass. | 1962 | Died on Aug. 25, 2009 | Scott P. Brown, R-Mass. - Elected Jan. 19, 2010 |
| Hillary Rodham Clinton, D-N.Y. | 2000 | Resigned from office effective Jan. 21, 2009 | Kirsten Gillibrand, D-N.Y. - Appointed Jan. 27, 2009 |
| Ken Salazar, D-Colo. | 2004 | Resigned from office effective Jan. 21, 2009 | Michael Bennet, D-Colo. - Appointed Jan. 22, 2009 |
| Joseph R. Biden Jr., D-Del. | 1972 | Biden resigned to become vice president. | Ted Kaufman, D-Del. - Appointed Jan. 16, 2009 |
| Barack Obama, D-Ill. | 2004 | Resigned from office effective Nov. 16, 2008 | Roland W. Burris, D-Ill. - Appointed Jan. 15, 2009 |
| House | | | |
| Robert Wexler, D-Fla. | 1996 | Resigned from office effective Jan. 3, 2010 | -- |
| John M. McHugh, R-N.Y. | 1992 | Resigned from office effective Sept. 21, 2009 | Bill Owens, D-N.Y. - Elected Nov. 3, 2009 |
| Ellen O. Tauscher, D-Calif. | 1996 | Resigned from office effective June 26, 2009 | John Garamendi, D-Calif. - Elected Nov. 3, 2009 |
| Hilda L. Solis, D-Calif. | 2000 | Resigned from office effective Feb. 24, 2009 | Judy Chu, D-Calif. - Elected July 14, 2009 |
| Kirsten Gillibrand, D-N.Y. | Appointed: 2009 | Senate | Scott Murphy, D-N.Y. - Elected March 31, 2009 |
| Name | First Elected | Announced |
| Senate | | |
| Ted Kaufman, D-Del. | 2008 | Kaufman announced he would not seek election in 2010 following his appointment to the seat |
| George LeMieux, R-Fla. | 2009 | LeMieux announced he would not seek election in 2010 following his appointment to the seat |
| Christopher J. Dodd, D-Conn. | 1980 | Jan. 6, 2010 |
| Byron L. Dorgan, D-N.D. | 1992 | Jan. 5, 2010 |
| Jim Bunning, R-Ky. | 1998 | July 27, 2009 |
| Roland W. Burris, D-Ill. | 2008 | Burris announced he would not seek election in 2010 following his appointment to the seat |
| Judd Gregg, R-N.H. | 1992 | Feb. 12, 2009 |
| George V. Voinovich, R-Ohio | 1998 | Jan. 12, 2009 |
| Christopher S. Bond, R-Mo. | 1986 | Jan. 8, 2009 |
| House | | |
| Steve Buyer, R-Ind. (4) | 1992 | Jan. 29, 2010 |
| Marion Berry, D-Ark. (1) | 1996 | Jan. 25, 2010 |
| Vic Snyder, D-Ark. (2) | 1996 | Jan. 15, 2010 |
| John Shadegg, R-Ariz. (3) | 1994 | Jan. 14, 2010 |
| Henry E. Brown Jr., R-S.C. (1) | 2000 | Jan. 4, 2010 |
| George Radanovich, R-Calif. (19) | 1994 | Dec. 29, 2009 |
| Bart Gordon, D-Tenn. (6) | 1984 | Dec. 14, 2009 |
| Brian Baird, D-Wash. (3) | 1998 | Dec. 9, 2009 |
| John Tanner, D-Tenn. (8) | 1988 | Dec. 1, 2009 |
| Dennis Moore, D-Kan. (3) | 1998 | Nov. 23, 2009 |
| Name | First Elected | Details |
| Senate | | |
| Sam Brownback, R-Kan. | 1996 | governor |
| Kay Bailey Hutchison, R-Texas | 1993 | governor |
| House | | |
| Mary Fallin, R-Okla. (5) | 2006 | governor |
| John Boozman, R-Ark. (3) | 2001 | Senate |
| Michael N. Castle, R-Del. (AL ) | 1992 | Senate |
| Charlie Melancon, D-La. (3) | 2004 | Senate |
| Joe Sestak, D-Pa. (7) | 2006 | Senate |
| Mark Steven Kirk, R-Ill. (10) | 2000 | Senate |
| Nathan Deal, R-Ga. (9) | 1992 | governor |
| J. Gresham Barrett, R-S.C. (3) | 2002 | governor |
| Roy Blunt, R-Mo. (7) | 1996 | Senate |
| Artur Davis, D-Ala. (7) | 2002 | governor |
| Paul W. Hodes, D-N.H. (2) | 2006 | Senate |
| Adam H. Putnam, R-Fla. (12) | 2000 | Fla. Agriculture commissioner |
| Todd Tiahrt, R-Kan. (4) | 1994 | Senate |
| Kendrick B. Meek, D-Fla. (17) | 2002 | Senate |
| Zach Wamp, R-Tenn. (3) | 1994 | governor |
| Jerry Moran, R-Kan. (1) | 1996 | Senate |
| Peter Hoekstra, R-Mich. (2) | 1992 | governor |