The eighteenth season of the American television medical drama Grey's Anatomy was ordered on May 10, 2021, by the American Broadcasting Company (ABC). It premiered on September 30, 2021, for the 2021–22 broadcast season. The season is produced by ABC Signature, in association with Shondaland Production Company and Entertainment One Television; the showrunner being Krista Vernoff.
 This is the first season not to feature Jesse Williams, Giacomo Gianniotti, and Greg Germann as series regulars since the seventh, twelfth, and sixteenth seasons, respectively. The season marked the return of Kate Walsh as Addison Montgomery for three episodes, after her last appearance on the season 8 episode "If/Then". On January 10, 2022, ABC renewed the series for a nineteenth season.
 The number in the "No. overall" column refers to the episode's number within the overall series, whereas the number in the "No. in season" column refers to the episode's number within this particular season. "U.S. viewers in millions" refers to the number of Americans in millions who watched the episodes live.
 As she ponders what to do with her life after surviving COVID-19, Meredith travels to the Mayo Clinic in Minnesota to attend the opening of a library dedicated to her mother. While there, she reconnects with Dr. Nick Marsh, whom she treated years ago. Dr. David Hamilton, a former colleague of her mother's, reveals his plan to open up a state-of-the-art research center dedicated to curing Parkinson's disease, with Meredith as the project's public face to attract talent. After his youngest son's panic attacks, Hayes connects with Bailey as they interview candidates to replace Jackson and Tom, as well as Jo, who is adjusting to life as a single mother and OB/GYN resident with Levi's help. Following her rejection of his proposal, Amelia and Link struggle to maintain their relationship, while Maggie and Winston enjoy their honeymoon phase. Owen and Teddy tie the knot in Joe's bar with a newly single Megan officiating after their planned ceremony in the park is ruined by a tandem bike crashing into the priest.
 A gas pipeline explosion sends injured bystanders to Grey Sloan, including Station 19 firefighter Vic Hughes, who doesn't realize that another firefighter, Dean Miller, has been killed by the explosion. Owen, who is working with Teddy on their burn-pit study, is thrown into a PTSD-induced panic attack due to the explosion, though it later only heightens his passion for his current work with veterans. Winston and Hayes perform heart surgery on Megan's son, Farouk, and Ben nervously tells Bailey that, since Dean has now passed, Ben and Bailey are legally responsible to raise Pru, Dean's daughter, due to a promise Ben made to Dean. In Minnesota, Meredith brings Tom Koracick on board, who is revealed to have a difficult past with Dr. Hamilton. Amelia gets closer with another member of the project, Dr. Kai Bartley, and Meredith and Nick further their relationship. 
 On March 25, 2021, Krista Vernoff, who serves as the showrunner and executive producer of Grey's Anatomy and Station 19 signed a two-year deal with ABC to remain on both series through a potential nineteenth season. The deal also keeps Trip the Light Productions, Vernoff's production company, attached to the series. Although no longer writing for the series, after her departure from ABC to Netflix in 2017, series creator Shonda Rhimes remains credited as a showrunner and executive producer. When ABC revealed its schedule for the 2021–22 broadcast season it was announced that the series would hold its previous time slot of Thursdays at 9:00 PM ET, with Station 19 serving as a lead-in. ABC announced its holiday programming schedule in October 2021, where it was revealed that the season would contain both a Thanksgiving and Christmas themed episode to air in November and December, respectively. The season finale was also the series' 400th episode.
 Kim Raver, Camilla Luddington, and Kevin McKidd each signed a three-year contract in July 2020 keeping them attached to the series through a potential nineteenth season to portray Dr. Teddy Altman, Dr. Jo Wilson, and Dr. Owen Hunt, respectively. The series remaining three original actors Ellen Pompeo, Chandra Wilson, and James Pickens, Jr., who portray Dr. Meredith Grey, Dr. Miranda Bailey, and Dr. Richard Webber, respectively, were all confirmed to be returning for the season. Pompeo signed a one-year contract for her return receiving over US$575,000 per episode and also making her the highest paid actress on broadcast television. Her contract also allows her to retain a producer credit on the series as well as co-executive producer credit on Station 19. Wilson and Pickens reportedly received a significant pay increase from their previous contracts. Giacomo Gianniotti, Jesse Williams, and Greg Germann did not return as series regulars to portray Dr. Andrew DeLuca, Dr. Jackson Avery, and Dr. Tom Koracick, respectively, after departing in the previous season. Meanwhile, Scott Speedman was added to the main cast as Dr. Nick Marsh, a character he had previously portrayed in the fourteenth season as a guest star.
 Former series regular Kate Walsh, who also headlined her own spin-off series entitled Private Practice from 2007 until 2013, returned to the series in a recurring capacity. Walsh, who portrays the character Dr. Addison Montgomery, returned in the third episode, "Hotter Than Hell", and had last guest starred in the eighth season episode "If/Then" in 2012. She then appeared in "With a Little Help From My Friends", the episode that immediately followed; and again in Should I Stay or Should I Go". Despite his departure in the seventeenth season, it was reported that Germann was expected to return in later seasons as a guest star which he later did, reprising his role in "Bottle Up and Explode!" and once more in "Legacy." Richard Flood departed as a series regular after the tenth episode of the season, "Living in a House Divided"; Flood was first introduced as a recurring character during the sixteenth season and was promoted to the main cast beginning with the seventeenth. Williams, who previously departed alongside Germann, stated in an interview that he would be open to returning during the season as well. In April 2022 it was confirmed that Williams would return to the series in the season finale alongside former co-star Sarah Drew. Drew portrayed Dr. April Kepner beginning in the sixth season and held the role for nine seasons, eight as a series regular, before departing in the fourteenth season, and briefly returning in the previous season for Williams' departure.
 The season also featured the return of recurring cast members Kate Burton as Dr. Ellis Grey and Abigail Spencer as Dr. Megan Hunt, both of whom last appeared in the fifteenth season. New cast members to the series who were cast in recurring roles for the season include Peter Gallagher as Dr. David Hamilton, Lynn Chen as Dr. Michelle Lin, and Greg Tarzan Davis as Dr. Jordan Wright. E.R. Fightmaster, who had guest starred in the season’s second and third episodes as Dr. Kai Bartley, was also promoted to a recurring cast member. Fightmaster and their character Bartley are both non-binary, being the first non-binary actor and character on the series. Skylar Astin and Rome Flynn were cast in recurring roles for the second half of the season to portray Todd Eames, an environmental sciences expert, and Wendell Ndugu, the brother of Hill's character, respectively. Bianca A. Santos and Cedric Sanders were also cast in recurring roles to portray Kristen and Simon Clark, a "married couple in a dire medical situation," for three episodes of the season.
 At the 2nd Hollywood Critics Association TV Awards the season received a nomination for Best Broadcast Network Series, Drama. This award was ultimately won by This Is Us. The season was also awarded The ReFrame Stamp, a certification given to scripted television productions that hire "women or individuals of other underrepresented gender identities/expressions [...] in four out of eight key roles including writer, director, producer, lead, co-leads, and department heads."