Nancy was the beloved matriarch of the Hughes family, and has been around since the show began in April 1956. She was married for over 50 years to attorney Chris Hughes until his death. Though, in her younger years, she was often critical of her children's marital affairs, she still managed to forge a good relationship with all of them. Later in life, Nancy married Detective Dan McClosky with whom she had a wonderful, but all too brief marriage. Dan was diagnosed with Alzheimer's disease. She remained faithful to Dan throughout this terrible illness, helping him maintain his dignity before he died of a heart attack. Nancy has helped many of the residents of Oakdale through the years with her wise words and attentive ear.

Nancy Hughes's quiet suburban life was about to take some interesting turns starting in 1956. Still in mourning over the loss of her oldest daughter, who died swimming in a storm, Nancy, the wife of attorney Chris Hughes, became very protective of her other daughter Penny's close bond with Chris's sister, the unconventional Edie Hughes. The sisters-in-laws' disapproval of each other went both ways with Edie describing Nancy as overly opinionated and hopelessly provincial and Nancy looking down on Edie's single freewheeling lifestyle. Chris, the peacemaker, acted as a buffer between the two women and Penny, defending Edie and indulging Penny. Having just been named junior partner at the law firm of Lowell, Barnes, & Lowell, Chris would discover that Edie was carrying on an affair with his best friend, the married Jim Lowell. Incredulous, Chris pleaded with her to end the affair, so as not to destroy the Lowell marriage. However, Edith, to Chris's consternation, was in love with Jim and she had no intention of ending the affair. In addition to worrying about Edith's indiscretion, he also was shocked to receive word that his younger brother, John, was in jail. Feeling as if he let his younger siblings down, by marrying after completing his law degree rather than paying for their education, Chris tried to help the troubled John but was initially met with harsh resistance. However, Chris refused to give up on John, something Nancy couldn't understand since she viewed him as a troublemaker. Meanwhile, Edith's affair with Jim was becoming known by more and more people, including their father and Nancy. Now living with Chris and his family, Pa Hughes let his opinions on the affair be known, but Edith refused to listen to anyone. Things only got worse, with Jim's father, Chris's boss, Judge James Lowell, suffered a heart attack and Jim's wife, Nancy's best friend, Claire, attempting suicide. Though Chris tried to be as supportive of Edith as he could, despite the fact that he wanted her to back away for the good of the Lowell family, Nancy wasn't so understanding and hurt Chris with her condescending attitude toward Edie, demanding that Chris ask Edie to leave town. Though a longtime defender of Edie, Chris reluctantly asked her to leave; but Edie refused, despite how the affair was hurting the Lowell family. However, in the end, it became apparent that perhaps the Lowell marriage shouldn't be saved, especially when Claire herself realized that she never really loved Jim.

In the midst of all this, Nancy's three children were growing up. The oldest, Don, was about to graduate from high school and was madly in love with an older waitress named Janice Turner. Chris believed that, as parents, he and Nancy should do nothing...let the relationship run its course. However, Nancy disagreed. She thought the older Janice was totally wrong for Don. Nancy made her opinion perfectly clear to Don as well as Janice. Unfortunately, all Nancy accomplished was to alienate herself from Don. Don resented his mother's interference, so much that when she returned to town after a thirteen-week absence (to take care of her ill brother-in-law), he refused to see her. Despite Nancy's criticism, Don and Janice continued seeing each other until, as Chris predicted, the affair fizzled out when Don was in college. In addition to Don, the Hugheses also had to deal with their teenage daughter, Penny. Nancy disapproved of Penny's new relationship with a spoiled young man named Jeff Baker. Believing that Nancy loved her deceased sister, Susan, more than her, an insecure Penny used to confide in her Aunt Edie. That was until she learned about the affair. Learning that her aunt was responsible for the breakup of the Lowell marriage, thus hurting Penny's best friend, Ellen, Penny turned her back on her favorite aunt. Confused and hurt, she rebelled and starting seeing more and more of Jeff, openly defying Nancy. Though Chris and his Pa couldn't condone Penny's hostile attitude toward Nancy, they realized that Nancy's self-righteousness was driving a wedge in the family. Then Penny and Jeff suddenly eloped. Chris and Nancy weren't at all happy that their underage daughter eloped and they forced an annulment, telling the couple to wait until Penny was of age. Not long after, Chris successfully defended Jeff when he was charged with killing Al James, who'd died in fight with Jeff. However, Nancy wasn't pleased to see Chris bonding with Jeff, since she thought the older and more responsible Tom Pope was a better choice for Penny. Despite Nancy's wishes, Penny's heart belonged to Jeff and, a year after they first eloped; Chris was very pleased to walk Penny down the aisle. Rounding out the Hughes family was their teenage son, Bob, a happy uncomplicated kid.

Meanwhile, Bob was growing up and had decided to become a doctor. Later, the Hugheses were shocked when he came home with a young woman named Lisa Miller and announced that they'd eloped. Not liking the idea of Bob marrying a woman they never even met, Chris and Nancy demanded that the couple get an annulment...that was until one thing changed everything: Lisa announced she was pregnant. In a reversal, Nancy accepted the union, while Chris was outraged and was ready to let the couple make their own way without any financial help from him. Luckily, Pa was able to persuade Chris to open his home to his son and new wife. Months later, Lisa gave birth to a son, Thomas Christopher Hughes. When Lisa had a tendency to be too busy having a social life to care for Tommy, and Bob was busy building his medical career, the job of raising Tommy tended to fall on Chris and Nancy. The years would bring more changes for the Hughes. In addition to dealing with the newly married Hugheses, Chris and Nancy also tried to help Penny, who to Nancy's disapproval had gotten a job as a writer. Chris was annoyed when Nancy kept pressuring Penny to divorce Jeff, who deserted her. Penny almost did, until suddenly Jeff returned. A changed man, Jeff had finally found his niche in life as a singer and, in time, Penny agreed to take him back. The one person Nancy wasn't glad to see back was Janice Turner Whipple, now a widow with two teenage daughters. Though her younger daughter, Alice, was a joy to have around, her oldest, Debbie was a terror since she was a sex-pot who smoked, lied, and ran with a fast crowd. Seeing Don renew his romance with Janice displeased Nancy to no end and she warned Don that he'd be making the biggest mistake of his life if he married her. Meanwhile, Lisa was far from the ideal daughter-in-law, making excuses as to why she couldn't do housework, spreading lies that Pa didn't like her and asking him to move out, and even manipulating Nancy into lecturing Bob about spending too much time at the hospital. To Chris's surprise, Nancy liked Lisa, seeing a spark in her that she admired, and formed a bond with her. In the midst of this, Jeff was killed in a car accident that left Penny with amnesia.

In addition to trying to help an amnesiac Penny, the family also had to deal with Bob's marriage to Lisa, which was about to end after Lisa told Bob she was leaving him for a rich salesman. Though Lisa tried to reunite with Bob, to Nancy's disappointment, Bob refused. Meanwhile, Nancy continued to alienate Don thanks to her attitude toward Janice. Finally, one day, in front of the entire family, Don accused Nancy of ostracizing his new family. Though Chris pleaded with Nancy to made amends, so they wouldn't lose their son, her attempts were blatantly half-hearted and, in disgust, Don and Janice left Oakdale. In the meantime, Penny's memory had returned and she found herself falling in love with Neil Wade. A few years later, the Hughes were shocked to learn that Janice had since died. Hurt that Don never told them, Chris wrote him a letter that Don promptly tore up. Resentful that he and Janice were denied years of happiness due to Nancy's interference while he was in high school, Don was finally persuaded by Judge Lowell to return to Oakdale, but remained distant. Happy to have his son back, Chris was infuriated when Nancy started inferring again by setting up Don with her new friend, Sara Fuller since he was afraid Don would leave again. Nancy had bonded with the independent woman so much that, to her family's surprise, the traditional Nancy offered to work part time in Sara's shop. This didn't sit too well with Pa who was used to Nancy's effectiveness in running the Hughes household. Then tragedy struck when Sara died in a fall. Though Chris suspected it was an accident, both Nancy and Don suspected that she was murdered by the daughter she gave up for adoption, Amanda Holmes. When Nancy agreed to act as a witness for the prosecution, Chris, as Amanda's lawyer, mercilessly grilled Nancy on the stand. Though this briefly caused Nancy to be so furious that she demanded he sleep on the couch, in the end Chris was able to prove that Sara's death was indeed accidental. Meanwhile, Bob had married a young woman named Sandy McGuire, who had been sent to jail for a crime she didn't commit. Though Chris liked Sandy, Nancy made no secret of the fact that she wanted Bob to remarry Lisa, even telling Sandy that she'd always consider Lisa to be her daughter-in-law.

The 1970s brought a period of change for the Hughes family. After becoming embroiled in drugs and falsely confessing to Shea's murder, Tom finally got his life together and started working at a medical clinic while studying law. It was at the medical clinic that he met a young woman named Meredith Harcourt who claimed to be too poor to pay her medical expenses. Though Tom fell for her story, even letting her stay at his place, Nancy felt that Meredith was misrepresenting herself; she seemed too “chic” to be a poor waif. Nancy's suspicions were confirmed when Meredith, trying to get on Nancy's good side, bought her a piece of “costume jewelry”. Suspicious, Nancy had it appraised and was shocked when it was valued at $2,000. Not long after, Don returned to town after Chris suffered a heart attack. Now that Don was back, Nancy decided to play matchmaker again and tried to set him up with nurse Jennifer Ryan, still hoping that a divorced Bob would reunite with Lisa. However, things weren't meant to be and Bob ended up falling for Jennifer. Unfortunately, Jennifer's son, Rick, deeply hated Bob. Though Nancy warned Bob that he'd be inheriting a problematic step-family if he married Jennifer, Bob didn't listen and married Jen anyway. Unfortunately, the marriage was a disaster due to arguments regarding Rick and Nancy only aggravated the situation by telling Jennifer that she'd foreseen this development all along. Later, when Jennifer became pregnant, Nancy sincerely tried to make amends, however Jennifer met her efforts with hostility. A few years after the birth of Jennifer's daughter, Frannie, Jennifer would be killed, leaving Nancy to help raise Frannie and regret how she'd treated Jennifer. A few years later, Don shocked the family by becoming involved with the scandalous Joyce Colman. Although Nancy disapproved, Chris warned her to keep her opinion to herself, for fear of losing their son again. This time, Nancy took his advice and kept mum. However, she still didn't entirely trust Joyce and when Joyce later ended up pregnant, a suspicious Nancy wondered if Don was the father, since he had been out of town for weeks. Nancy's suspicious would turn out to be correct, and Don would later divorce Joyce. Later, Nancy was quick to note that Don was falling in love with his secretary, Mary Ellison, and it appeared that the feeling was mutual. Not long after, the Hugheses would celebrate Don and Mary's marriage.

Though Chris and Nancy left Oakdale briefly to retire to Arizona, they returned for Bob's wedding to his long-time friend, Kim. Knowing that Chris was ill, Bob persuaded them to live with him. When the elder Hugheses refused, not wanting to be a burden, Bob converted the upper portion of his garage into an apartment. Not long after Chris and Nancy's celebrated their 50th wedding anniversary, Chris would pass away in his sleep.

A few years later, Nancy found herself courted by the Chief of the Oakdale Police, Dan McClosky, a widower himself, and the two made plans to marry. Although Bob, as well as Dan's daughter, Bernice, initially objected to them marrying, they came around, and Nancy married Dan in a beautiful ceremony at Bob's home. After Dan retired from the police force after suffering a heart attack, he began suffering from memory lapses and was diagnosed with Alzheimer's. Not one to shy away from adversity, Nancy vowed to stand by his side and support him. Since Dan's death of a heart attack, Nancy has lived a quiet life at Bob and Kim's, offering advice and a sympathetic ear to her family.

Recently, Nancy has provided guidance to the young people of Oakdale, first to teenager Allison Stewart and then to Tom's sister-in-law, Katie Peretti. In 2006, Katie anonymously wrote a novel called "Oakdale Confidential.” Unfortunately, the novel raised quite a bit of ire and, to take suspicion off herself, Katie begged Nancy to state that she was the one who wrote the novel. Nancy agreed and ended up getting some ire from Lisa in return since Lisa didn't like how she was portrayed in the book. After playing peacekeeper, Kim realized that Nancy wasn't the author after all, but Nancy refused to discuss it. Over a year later, Nancy was at Bob's bedside when he inexplicably fell into a coma. Thankfully, after six weeks, Bob woke up and made a full recovery. Months later, Nancy was on hand to help celebrate Tom and Margo's 25th anniversary.

Much of her screen time in 2006 found the character embroiled in a mystery surrounding the publication of a scandalous novel, "Oakdale Confidential," which shed light on the checkered pasts of several characters.

In 2009, Nancy is still active and works as a volunteer as the hospital. On Thanksgiving 2009, she gives pieces of advice to Katie after the death of Brad. Nancy again showed up just after Christmas when she heard of Casey's upcoming marriage to Alison. She gave him the engagement ring that Chris gave her. When the engagement was broken off, the ring was returned to Nancy, but she insisted that Casey hang onto it.

Nancy was on hand in 2010 to celebrate Bob and Kim's 25th wedding anniversary. Nancy and the rest of the family were all shocked to find out that they really weren't married. She helped Bob and Kim settle their recent differences and was delighted when Frannie returned to see them wed. In her final appearance on the series, Nancy is seen having breakfast with Casey and Alison, and yet again giving advice to Katie on coping with Brad's death.