| Res. | Record | Opponent | Method | Event | Date | Round | Time | Location | Notes |
| Win | 26–5 | Rafael Fiziev | Decision (unanimous) | UFC 313 | March 8, 2025 | 3 | 5:00 | Las Vegas, Nevada, United States | Fight of the Night. |
| Loss | 25–5 | Max Holloway | KO (punch) | UFC 300 | April 13, 2024 | 5 | 4:59 | Las Vegas, Nevada, United States | Lost the symbolic UFC "BMF" title. Fight of the Night. |
| Win | 25–4 | Dustin Poirier | KO (head kick) | UFC 291 | July 29, 2023 | 2 | 1:00 | Salt Lake City, Utah, United States | Won the symbolic UFC "BMF" title. Performance of the Night. |
| Win | 24–4 | Rafael Fiziev | Decision (majority) | UFC 286 | March 18, 2023 | 3 | 5:00 | London, England | Fight of the Night. |
| Loss | 23–4 | Charles Oliveira | Submission (rear-naked choke) | UFC 274 | May 7, 2022 | 1 | 3:22 | Phoenix, Arizona, United States | For the vacant UFC Lightweight Championship. Oliveira missed weight (155.5 lb) and was stripped of the title. Only Gaethje was eligible to win the title. |
| Win | 23–3 | Michael Chandler | Decision (unanimous) | UFC 268 | November 6, 2021 | 3 | 5:00 | New York City, New York, United States | Fight of the Night. |
| Loss | 22–3 | Khabib Nurmagomedov | Technical Submission (triangle choke) | UFC 254 | October 24, 2020 | 2 | 1:34 | Abu Dhabi, United Arab Emirates | For the UFC Lightweight Championship. |
| Win | 22–2 | Tony Ferguson | TKO (punch) | UFC 249 | May 9, 2020 | 5 | 3:39 | Jacksonville, Florida, United States | Won the interim UFC Lightweight Championship. Performance of the Night. Fight of the Night. |
| Win | 21–2 | Donald Cerrone | TKO (punches) | UFC Fight Night: Cowboy vs. Gaethje | September 14, 2019 | 1 | 4:18 | Vancouver, British Columbia, Canada | Performance of the Night. |
| Win | 20–2 | Edson Barboza | KO (punch) | UFC on ESPN: Barboza vs. Gaethje | March 30, 2019 | 1 | 2:30 | Philadelphia, Pennsylvania, United States | Fight of the Night. |
| Win | 19–2 | James Vick | KO (punches) | UFC Fight Night: Gaethje vs. Vick | August 25, 2018 | 1 | 1:27 | Lincoln, Nebraska, United States | Performance of the Night. |
| Loss | 18–2 | Dustin Poirier | TKO (punches) | UFC on Fox: Poirier vs. Gaethje | April 14, 2018 | 4 | 0:33 | Glendale, Arizona, United States | Fight of the Night. Gaethje was deducted one point in round 3 due to repeated eye pokes. |
| Loss | 18–1 | Eddie Alvarez | KO (knee) | UFC 218 | December 2, 2017 | 3 | 3:59 | Detroit, Michigan, United States | Fight of the Night. |
| Win | 18–0 | Michael Johnson | TKO (punches and knees) | The Ultimate Fighter: Redemption Finale | July 7, 2017 | 2 | 4:48 | Las Vegas, Nevada, United States | Performance of the Night. Fight of the Night. |
| Win | 17–0 | Luiz Firmino | TKO (doctor stoppage) | WSOF 34 | December 31, 2016 | 3 | 5:00 | New York City, New York, United States | Defended the WSOF Lightweight Championship. |
| Win | 16–0 | Brian Foster | TKO (leg kicks) | WSOF 29 | March 12, 2016 | 1 | 1:43 | Greeley, Colorado, United States | Defended the WSOF Lightweight Championship. |
| Win | 15–0 | Luis Palomino | TKO (punches) | WSOF 23 | September 18, 2015 | 2 | 4:30 | Phoenix, Arizona, United States | Defended the WSOF Lightweight Championship. |
| Win | 14–0 | Luis Palomino | TKO (leg kicks and punches) | WSOF 19 | March 28, 2015 | 3 | 3:57 | Phoenix, Arizona, United States | Defended the WSOF Lightweight Championship. |
| Win | 13–0 | Melvin Guillard | Decision (split) | WSOF 15 | November 15, 2014 | 3 | 5:00 | Tampa, Florida, United States | Non-title bout; Guillard missed weight (158.8 lb). |
| Win | 12–0 | Nick Newell | TKO (punches) | WSOF 11 | July 5, 2014 | 2 | 3:09 | Daytona Beach, Florida, United States | Defended the WSOF Lightweight Championship. |
| Win | 11–0 | Richard Patishnock | TKO (punches and elbows) | WSOF 8 | January 18, 2014 | 1 | 1:09 | Hollywood, Florida, United States | Won the inaugural WSOF Lightweight Championship. |
| Win | 10–0 | Dan Lauzon | KO (punches) | WSOF 6 | October 28, 2013 | 2 | 1:40 | Coral Gables, Florida, United States | |
| Win | 9–0 | Brian Cobb | TKO (leg kicks) | WSOF 3 | June 14, 2013 | 3 | 2:19 | Las Vegas, Nevada, United States | |
| Win | 8–0 | Gesias Cavalcante | TKO (doctor stoppage) | WSOF 2 | March 23, 2013 | 1 | 2:27 | Atlantic City, New Jersey, United States | |
| Win | 7–0 | Adrian Valdez | TKO (punches) | Rage in the Cage 164 | November 16, 2012 | 2 | 0:19 | Chandler, Arizona, United States | |
| Win | 6–0 | Drew Fickett | KO (punch) | Rage in the Cage 163 | October 20, 2012 | 1 | 0:12 | Chandler, Arizona, United States | Catchweight (165 lb) bout. |
| Win | 5–0 | Sam Young | Submission (rear-naked choke) | Rage in the Cage 162 | September 29, 2012 | 2 | 1:58 | Chandler, Arizona, United States | |
| Win | 4–0 | Marcus Edwards | Decision (unanimous) | Ring of Fire 43 | June 2, 2012 | 3 | 5:00 | Broomfield, Colorado, United States | |
| Win | 3–0 | Donnie Bell | TKO (punches) | Ring of Fire 42 | December 17, 2011 | 2 | 2:57 | Broomfield, Colorado, United States | |
| Win | 2–0 | Joe Kelso | TKO (punches) | Bring the Thunder MMA 2 | October 1, 2011 | 1 | 4:32 | Pueblo, Colorado, United States | Lightweight debut. |
| Win | 1–0 | Kevin Croom | KO (slam) | Ring of Fire 41 | August 20, 2011 | 1 | 1:01 | Broomfield, Colorado, United States | Catchweight (159 lb) bout. |