| # | Weekend end date | Film | Studio | Box office |
| 1 | January 7, 2021 | Wonder Woman 1984 | Warner Bros. Pictures, DC Films, Atlas Entertainment, & The Stone Quarry | $56,658 |
| 2 | January 14, 2021 | Greenland | Anton, Thunder Road, G-BASE Film Production, & Riverstone Pictures | $49,563 |
| 3 | January 21, 2021 | $52,351 |
| 4 | January 28, 2021 | $71,914 |
| 5 | February 4, 2021 | $69,532 |
| 6 | February 11, 2021 | Tom & Jerry † | Warner Animation Group, The Story Company, & Turner Entertainment Co. | $179,315 |
| 7 | February 18, 2021 | $187,225 |
| 8 | February 25, 2021 | $221,066 |
| 9 | March 4, 2021 | $168,200 |
| 10 | March 11, 2021 | $150,262 |
| 11 | March 18, 2021 | $121,936 |
| 12 | March 25, 2021 | Raya and the Last Dragon | Walt Disney Animation Studios | $24,205 |
| 13 | April 1, 2021 | Godzilla vs. Kong | Legendary Pictures | $520,396 |
| 14 | April 8, 2021 | $153,105 |
| 15 | April 15, 2021 | $71,886 |
| 16 | April 22, 2021 | Mortal Kombat | New Line Cinema & Atomic Monster | $68,342 |
| 17 | April 29, 2021 | $21,287 |
| 18 | May 6, 2021 | $43,836 |
| 19 | May 13, 2021 | Those Who Wish Me Dead | New Line Cinema, Bron Studios, Film Rites, & Bosque Ranch Productions | $72,427 |
| 20 | May 20, 2021 | The Unholy | Screen Gems & Ghost House Pictures | $206,491 |
| 21 | May 27, 2021 | Cruella | Walt Disney Pictures, Marc Platt Productions, Gunn Films | $251,549 |
| 22 | June 3, 2021 | The Conjuring: The Devil Made Me Do It | New Line Cinema, Atomic Monster, & The Safran Company | $960,560 |
| 23 | June 10, 2021 | $554,607 |
| 24 | June 17, 2021 | Cruella | Walt Disney Pictures, Marc Platt Productions, Gunn Films | $132,271 |
| 25 | June 24, 2021 | F9 | Universal Pictures, Original Film, One Race Films, Perfect Storm Entertainment, Roth/Kirschenbaum Films | $1,775,000 |
| 26 | July 1, 2021 | Cruella | Walt Disney Pictures, Marc Platt Productions, Gunn Films | $62,301 |
| 27 | July 8, 2021 | Black Widow | Marvel Studios | $793,874 |
| 28 | July 15, 2021 | Space Jam: A New Legacy | Warner Animation Group, Proximity Media, & The SpringHill Company | $680,119 |
| 29 | July 22, 2021 | $431,413 |
| 30 | July 29, 2021 | Jungle Cruise | Walt Disney Pictures, Davis Entertainment, Seven Bucks Productions, & Flynn Picture Company | $389,217 |
| 31 | August 5, 2021 | The Suicide Squad | DC Films, Atlas Entertainment, & The Safran Company | $429,063 |
| 32 | August 12, 2021 | Free Guy | Berlanti Productions, 21 Laps Entertainment, Maximum Effort, Lit Entertainment Group, & TSG Entertainment | $262,359 |
| 33 | August 19, 2021 | $185,458 |
| 34 | August 26, 2021 | $54,490 |
| 35 | September 2, 2021 | Shang-Chi and the Legend of the Ten Rings | Marvel Studios | $586,434 |
| 36 | September 9, 2021 | $448,273 |
| 37 | September 16, 2021 | $341,030 |
| 38 | September 23, 2021 | $192,085 |
| 39 | September 30, 2021 | No Time to Die | Metro-Goldwyn-Mayer & Eon Productions | $507,047 |
| 40 | October 7, 2021 | Venom: Let There Be Carnage | Columbia Pictures, Marvel Entertainment, Arad Productions, Matt Tolmach Productions, & Pascal Pictures | $872,686 |
| 41 | October 14, 2021 | $864,850 |
| 42 | October 21, 2021 | $420,808 |
| 43 | October 28, 2021 | $310,273 |
| 44 | November 4, 2021 | Eternals | Marvel Studios | $1,209,533 |
| 45 | November 11, 2021 | $633,903 |
| 46 | November 18, 2021 | $330,936 |
| 47 | November 25, 2021 | Encanto | Walt Disney Animation Studios | $2,797,869 |
| 48 | December 2, 2021 | $1,980,677 |
| 49 | December 9, 2021 | $1,270,027 |
| 50 | December 16, 2021 | Spider-Man: No Way Home | Columbia Pictures, Marvel Studios, & Pascal Pictures | $3,272,812 |
| 51 | December 23, 2021 | $1,376,904 |
| 52 | December 30, 2021 | $747,709 |
