Best friends, Will, who is a gay lawyer, and interior designer Grace, share an apartment and are constantly in each other's business. Stirring the pot of melodrama is Grace's "employee," Karen, and Jack, Will's flamboyant friend.
Will and Jack visit Jack's grandson, Skip, in Texas to watch him perform at his church's talent show. But when Jack learns Skip plans on singing "Diamonds Are A Girl's Best Friend," he becomes afraid for his grandson's safety. Karen tags along to check out the portion of the border wall she sponsored, only to discover that Beverley Leslie has claimed it as his own. Back home, Grace and Noah try to figure out if something is wrong in their relationship because their numerous attempts to have sex have failed.
Will discovers that Noah has a child he hasn't told Grace about, but is now sworn to secrecy. Karen and Jack's relationship is tested when she fires him from the play she's producing and replaces him with Jon Cryer.
Grace unintentionally meets Noah's daughter Katie; Will's mom Marilyn visits after the death of her beloved dog, but doesn't get the emotional support she expects; Jack argues with his rec center boss, Theo.
In order to land a handsome, gay TV news anchor with a pension for dim, frothy men, Jack convinces Will to not be himself and to act like someone silly and stupid. Karen learns that her alimony will be severely limited unless she can get photos of her ex-husband's affair with Lorraine Finster, so she enlists Grace to go with her to the strip club where Lorraine works. Olympian Adam Rippon has a cameo as a barista with an attitude.
Will, Karen and Jack unknowingly take hallucinogens, which cause Will and Jack to wonder whether they're soul mates and have Karen giving her final performance as Mrs. Stanley Walker; a high-powered client takes up with Grace's sister Janet.
Will and Grace's plan to win over Will's new Columbia department head goes awry when he drops dead in their apartment - and they use his phone to text his full recommendation of Will. Karen and Estefan's dislike for each other puts Jack in full damage control mode when he must keep them separate at his birthday dinner.
When Will discovers Karen's estranged stepdaughter Olivia is a student in his law class, he attempts to solve their issues with a mock trial. Grace and Jack go on a diet together, but giving up their eating habits proves harder than anticipated.
Malcolm enlists Grace to help him win back Karen's affections. Will's flirtation at work lands him in an ethical dilemma.Jack's passion for performing is reignited by a chance encounter with Zusanna, the sister of his former acting teacher.
Will gives local newscaster McCoy Whitman a second chance and, with the help of Jack, finally gets to know the man behind the newsman. Grace's campaign for Design Guild President hits a snag when the deciding vote comes down to her old nemesis, Val. Karen acts as Grace's campaign manager, and attempts to secure Val's vote by any means necessary.
Jack's insistence that Will be nicer to his fiancé, Estefan, backfires when Estefan thinks Will is in love with him. In a hurry to buy her boyfriend Noah a Valentine's Day gift, Grace unknowingly knocks over a prominent figure while going after a taxi. And when Karen discovers that Noah not only writes her favorite romance novels but also plans to kill off the main character, she forces him to rewrite the story.
After her dad, Martin, is rushed to the hospital, Grace is shocked when he refuses a transfusion of Will's blood. Will's mom, Marilyn, uncharacteristically takes Martin to task. Karen's demands cause Jack to uninvite her to his wedding.
When both of their boyfriends ask to move in, Will and Grace use each other as an excuse to get out of it. A snowstorm traps Karen at the office and Jack in an elevator, where he reunites with old flame Drew and tests his commitment to monogamy.
Jack realizes he lost 13 gold coins he's supposed to give Estefan at their wedding to avoid a curse. Will is concerned that Grace is the only one compromising in her relationship with Noah. Karen shows up at a dinner party with her new date, Nikki.