These are the number-one hits on the Top 100 Singles chart in 1981 as published by Cash Box magazine.
| Indicates best-performing single of 1981 |
| Issue date | Song | Artist | |
|---|---|---|---|
| January 3 | "(Just Like) Starting Over" | John Lennon | |
| January 10 | |||
| January 17 | |||
| January 24 | |||
| January 31 | "The Tide Is High" | Blondie | |
| February 7 | |||
| February 14 | "Celebration" | Kool & the Gang | |
| February 21 | "I Love a Rainy Night" | Eddie Rabbitt | |
| February 28 | "9 to 5" | Dolly Parton | |
| March 7 | "Keep on Loving You" | REO Speedwagon | |
| March 14 | "Woman" | John Lennon | |
| March 21 | |||
| March 28 | "Rapture" | Blondie | |
| April 4 | |||
| April 11 | "Kiss on My List" | Daryl Hall and John Oates | |
| April 18 | "Morning Train (Nine to Five)" | Sheena Easton | |
| April 25 | |||
| May 2 | |||
| May 9 | |||
| May 16 | |||
| May 23 | "Being With You" | Smokey Robinson | |
| May 30 | "Bette Davis Eyes" | Kim Carnes | |
| June 6 | |||
| June 13 | |||
| June 20 | "Medley: Intro Venus / Sugar Sugar / No Reply / I'll Be Back / Drive My Car / Do You Want To Know a Secret / We Can Work It Out / I Should Have Known Better / Nowhere Man / You're Going To Lose That Girl / Stars on 45" | Stars on 45 | |
| June 27 | |||
| July 4 | "Bette Davis Eyes" | Kim Carnes | |
| July 11 | |||
| July 18 | "The One That You Love" | Air Supply | |
| July 25 | "Jessie's Girl" | Rick Springfield | |
| August 1 | "Elvira" | Oak Ridge Boys | |
| August 8 | "Theme From “Greatest American Hero" | Joey Scarbury | |
| August 15 | bgcolor=#FFFF99 rowspan="9" | "Endless Love" | Diana Ross and Lionel Richie |
| August 22 | |||
| August 29 | |||
| September 5 | |||
| September 12 | |||
| September 19 | |||
| September 26 | |||
| October 3 | |||
| October 10 | |||
| October 17 | "Arthur's Theme (Best That You Can Do)" | Christopher Cross | |
| October 24 | |||
| October 31 | |||
| November 7 | |||
| November 14 | "Private Eyes" | Daryl Hall and John Oates | |
| November 21 | "Physical" | Olivia Newton-John | |
| November 28 | |||
| December 5 | |||
| December 12 | |||
| December 19 | |||
| December 26 | |||