Will Truman, a gay man and lawyer, lives with his best friend Grace Adler, a Jewish woman who runs her own interior design firm. Their friends are Karen Walker, a rich socialite, and Jack McFarland, a struggling actor/singer/dancer who also has had brief careers as an acting teacher, back-up dancer, cater-waiter, talk-show host and student nurse.
Grace's accidental run-in with Noah, a curmudgeonly man she follows on Twitter, hints at a possible new love interest. Jack wants to look younger before meeting Estefan's family on Skype but makes a terrible first impression after overdoing the numbing cream before his facial procedure. Meanwhile, Will helps Karen protect the intellectual property rights of her most prized possession.
Will, Grace, and Jack are upset when they discover they’ve been too preoccupied with the changes in their own lives: Will teaching law at Columbia, Grace running for president of the New York Interior Designers Society and Jack’s new relationship with Estefan to even notice Karen has not been seen in days – ever since her husband found out about her affair with Malcolm.
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. Grace and Noah try to figure out if something is wrong in their relationship because their attempts to have sex have failed.
Will and Grace discover old letters written to each other from their college days, and decide to read them together. But reminiscing about the past turns ugly when a major bombshell is revealed in one of the letters. Meanwhile, when Karen announces she'll never fall in love again, Jack channels Rosario - or does he? - to convince her it's never too late to find love
Grace joins her father on a road trip, and a secret from her past is finally revealed, causing father and daughter to address something that will change their relationship forever. Meanwhile, Will, Karen, and Jack celebrate Jack's engagement at a gay bar run by legendary drag queen Miss Coco Peru. When it's revealed that Jack has chosen both of them to be his best man, Will and Karen have a lip-sync monologue throwdown to determine who truly deserves the coveted title.
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 TV news anchor with a penchant for dim, silly men, Will seeks advice from Jack on how not to be himself; Karen enlists Grace to help get photos of her ex Stan's affair with Lorraine Finster.
Will, Karen and Jack unknowingly take a hallucinogenic drug, which causes Will and Jack to wonder if they're each other's soul mate and has Karen giving her last "performance" as Mrs. Stanley Walker. Meanwhile, Grace is shocked when her high-powered client takes up with her 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.
Will and Grace both falter when their political beliefs are put to the test; and Jack and Karen help them hide their secret shame from each other, but the truth finally comes out.
Will and Jack try to date younger guys but find it challenging. Grace and Karen experience a crisis that reveals Grace's true feelings about Karen.
Grace is shocked to find that the emergency contact called by her doctor's office is ex-husband Leo, not Will. Jack takes on a new job he never expected to love. Karen befriends a 12-year-old girl in the Bronx, despite her best efforts.
Jack is stunned to learn that his estranged son, Elliot has a son of his own, Skip. Moreover, Skip needs the kind of help only Will and Jack can provide. Grace and Karen behave badly with the hot new guy at work.
Grace tries for her biggest job yet: decorating a string of boutique hotels for an obnoxious mogul. Meanwhile, Will is surprised at his reaction to making Senior Partner; Beverley Leslie discloses his secret to Karen; and Jack owns half of a winning lottery ticket.
When Karen has trouble dealing with a personal tragedy, Will, Grace, and Jack try to intervene. Will and Grace's new business relationship begins to show signs of stress.
Will, Grace, Karen, and Jack wish they could have experienced Christmas in old New York City, but realize the past was not quite as romantic -- or open to diversity -- as they pictured it.
Will and Grace try to convince themselves they are okay with dating the same man; Jack and Karen get an annoying commercial jingle stuck in their heads and must seek medical attention.
Will and Grace's old friend Larry decides he's in love with Will. On Jack's first day as a Lyft driver, he hits his wacky neighbor Val. Karen steps in to bail out Jack, but then needs Jack to bail her out.
Will, Grace, Jack and Karen attend the wedding of Will's ex-boyfriend, Vince. While Grace tries to keep Will from making a scene, Jack learns that his wedding hookup has many strings attached.
Jack's intimacy issues are challenged by a closeted boyfriend; Will and Grace sell their new line of bedding on live television.
Grace is horrified to realize that she's dated three men from the same family; Will and Karen get on each other's nerves at the office until they bond over watching -- and producing -- their own little telenovela.
A baby shower makes Grace and Will question their life choices; Karen and Jack find a way to combine child labor with musical theater.
Against Jack's advice, Will rekindles a relationship with his first love; Grace reluctantly fights for Karen's civil rights when a bakery refuses to make a cake she wants.
Grace brings Will for support when she goes home to celebrate her deceased mother's birthday; Jack's faith in love is crushed after a breakup; a secret in Karen's marriage is uncovered.