| Senator | 2012 (Current) District | Running in 2022 (New) District |
| Michael J. Barrett (D), Lexington | Third Middlesex | Third Middlesex |
| Michael Brady (D), Brockton | Second Plymouth & Bristol | Second Plymouth & Norfolk |
| William Brownsberger (D), Belmont | Second Suffolk & Middlesex | Suffolk & Middlesex |
| Harriette Chandler (D), Worcester *Not running for reelection –>Succeeded by Robyn K. Kennedy (D), Worcester | First Worcester | First Worcester |
| Sonia Chang-Diaz, (D), Boston *Not Running for Reelection –>Succeeded by Liz Miranda (D), Boston | Second Suffolk | Second Suffolk |
| Nick Collins (D), Boston | First Suffolk | First Suffolk |
| Joanne Comerford (D), Amherst | Hampshire, Franklin & Worcester | Hampshire, Franklin & Worcester |
| Cynthia Stone Creem (D), Newton | First Middlesex & Norfolk | Norfolk & Middlesex |
| Brendan Crighton (D), Lynn | Third Essex | Third Essex |
| John Cronin (D) Lunenburg | Worcester & Middlesex | Worcester & Middlesex |
| Julian A. Cyr (D), Truro | Cape & Islands | Cape & Islands |
| Sal N. DiDomenico (D), Everett | Middlesex & Suffolk | Middlesex & Suffolk |
| Diane DiZoglio (D), Methuen *Not running for reelection –>Succeeded by Pavel Payano (D), Lawrence | First Essex | First Essex |
| Lydia Edwards (D) | First Suffolk & Middlesex | Third Suffolk |
| James B. Eldridge (D), Acton | Middlesex & Worcester | Middlesex & Worcester |
| Ryan Fattman (R), Webster | Worcester & Norfolk | Worcester & Hampden |
| Paul Feeney (D), Walpole | Bristol & Norfolk | Bristol & Norfolk |
| Barry Finegold (D), Andover | Second Essex & Middlesex | Second Essex & Middlesex |
| Cindy Friedman (D), Arlington | Fourth Middlesex | Fourth Middlesex |
| Anne M. Gobi (D), Spencer | Worcester, Hampden, Hampshire & Middlesex | Worcester & Hampshire |
| Adam Gomez (D), Springfield | Hampden | Hampden |
| Adam G. Hinds (D) Pittsfield, *Not running for reelection –>Succeeded by Paul W. Mark (D), Foxborough | Berkshire, Hampshire, Franklin & Hampden | Berkshire, Hampden, Franklin & Hampshire |
| Patricia D. Jehlen (D), Somerville | Second Middlesex | Second Middlesex |
| John F. Keenan (D), Quincy | Norfolk & Plymouth | Norfolk & Plymouth |
| Edward Kennedy (D), Lowell | First Middlesex | First Middlesex |
| Eric Lesser (D), Longmeadow *Not running for reelection –>Succeeded by Jacob R. Oliveira (D), Ludlow | First Hampden & Hampshire | Hampden, Hampshire & Worcester |
| Jason Lewis (D) Winchester | Fifth Middlesex | Fifth Middlesex |
| Joan Lovely (D), Salem | Second Essex | Second Essex |
| Mark C. Montigny (D), New Bedford | Second Bristol & Plymouth | Second Bristol & Plymouth |
| Michael O. Moore (D), Millbury | Second Worcester | Second Worcester |
| Susan Moran (D) Falmouth | Plymouth & Barnstable | Plymouth & Barnstable |
| Patrick O’Connor (R), Weymouth | Plymouth & Norfolk | First Plymouth & Norfolk |
| Marc R. Pacheco (D), Taunton | First Plymouth & Bristol | Third Bristol & Plymouth |
| Rebecca Rausch (D), Wrentham | Norfolk, Bristol & Middlesex | Norfolk, Worcester & Middlesex |
| Michael J. Rodrigues (D), Westport | First Bristol & Plymouth | First Bristol & Plymouth |
| Michael F. Rush (D), Boston | Norfolk & Suffolk | Norfolk & Suffolk |
| Karen E. Spilka (D), Ashland | Second Middlesex & Norfolk | Middlesex & Norfolk |
| Bruce E. Tarr (R), Gloucester | First Essex & Middlesex | First Essex & Middlesex |
| Walter Timility (D), Milton | Norfolk, Bristol & Plymouth | Norfolk, Plymouth & Bristol |
| John Velis (D) Westfield | Second Hampden & Hampshire | Hampden & Hampshire |