Jeff Webber was first introduced in the spring of 1976 when he arrived in Port Charles after graduating from medical school. Jeff and his wife Monica Bard Webber planned to join the staff of General Hospital following in the footsteps of Jeff's older brother Rick who had joined GH two months before but had recently been killed in a plane crash over Africa. Steve Hardy tapped the young married Webbers for a bold new experimental program at the hospital called Mr. and Mrs. Intern. For Steve, the Mr. and Mrs. Intern experiment was a noble gamble. He believed that Jeff and Monica were a perfect choice. It was six months into their marriage and Steve assumed they were ideally happy. Steve was wrong. Their marriage was a wreck. Jeff had a major hang up. Jeff feared everyone at GH was comparing him to his dead brother Rick. Fearing he would always be 'second best', Jeff's every thought was plagued by memories of Rick. Jeff missed him dearly...and so did Monica. Before Monica married Jeff, she had once been engaged to Rick and she missed him more than anyone else knew.

Suddenly, Rick appeared alive. He wasn't dead at all. Rick had been captured by African revolutionaries during a civil war and held prisoner for ten months. Upon his return to GH, Rick was haunted by something. Many thought that it was the months of imprisonment Rick endured but to Rick's older sister Terri Arnett, he was troubled over the fact that Monica had married Jeff. Jeff was wary every time he saw Monica and Rick together. His jealously exploded into anger when he discovered that Monica had met Rick in New York before Rick returned to Port Charles. After seeing the troubles that Jeff and Monica were facing, Steve abandoned the Mr. and Mrs. Intern program. Meanwhile, Jeff didn't know that Monica and Rick had secretly confessed their love to each other but he had suspicions that the two were having an affair. Jeff's suspicions grew more fierce and he began to take pills to numb his pain. When Rick and Monica left town together for a hospital trip, a drunken Jeff became convicted the two were having an affair. He raced to their motel and barged into Monica's room expecting the find the two making love. However, only Monica was there. Jeff confronted Monica and the two had a bitter fight sending Monica into Rick's arms... and his bed. Jeff went back to Port Charles where he then had an affair with Heather Grant, a scheming nanny who wanted Jeff to herself.

Then, Heather became pregnant but didn't tell anyone; not even Jeff. Suddenly, Jeff disappeared. No one knew where he was. Rick was worried, Monica was frightened and Heather needed Jeff because she was pregnant with his baby. Jeff later showed up at a Port Charles bar called Barney's Place where he was drunk and high on amphetamines. Barney became nervous that Jeff would leave the bar and people would think he got that way while at the bar so he put Jeff in the back room overnight. Unknown to Barney, Jeff stole a gun that was kept in the back of the bar. Barney called Mark Dante to come pick Jeff up the next day but when Mark arrived he heard a gunshot and found Jeff unconscious with a bullet in his brain. Rick blamed himself and Terri feared that Jeff would die. Terri had a secret that had to be revealed before Jeff did pass away and it involved Steve Hardy. Terri went to Steve and told him that while her mother Helene was on her deathbed, she said that there was a letter in a safety deposit box that revealed that Steve was Jeff's father.

In 1977, Jeff had a slow recovery from his bullet wound and, out of guilt, Monica reconciled with him. Then, Heather revealed to Jeff that she was pregnant. When Jeff told Heather to abort the baby so that he could still be with Monica, Heather faked a suicide attempt to win Jeff's love to no avail. Heather then ordered Jeff to leave Monica but he wouldn't. This gave Heather the perfect scheme. Heather would move to New York and give birth to the baby and then sell it to Peter and Diana Taylor for $10,000. Heather did just that and Jeff wasn't the wiser, even after Heather told Jeff that the baby had died. Monica, meanwhile, was shaken by the fact that Rick had asked Lesley Faulkner to marry him and she asked Jeff for a divorce. On the rebound, Jeff asked Heather to marry him, especially after learning their child had died.

In 1978, Jeff and Heather married, but early into their marriage, the newlyweds saw very little of each other as Heather had become the nanny of her own child 'P.J. Taylor' and Jeff was studying for his license. Soon, Heather discovered that she was pregnant and Jeff announced that if the baby was a boy, he wanted to name him Steven Lars. Heather however lost the baby.

In the winter of 1979, Steve Hardy was forced to place General Hospital under quarantine due to an outbreak of the deadly Lassa Fever. Jeff, Steve, Rick, Alan, Audrey, and Monica were among the staff quarantined for a few weeks. After weeks, of work, Steve fell ill with the fatal disease. Believing that Steve was on his deathbed, Audrey told Jeff that Steve was his real father. Jeff was stunned and hurt by the news and was cold to Steve when he recovered. Meanwhile, Heather was obsessed to see her son whom she had sold to the Taylors. Heather planned to put LSD in Diana Taylor's drink and make her go insane. However the glasses were switched and Heather drank the LSD. She began to wildly hallucinate and Jeff had no choice but to ship her off to Pine Circle Sanitarium. It was then revealed that baby P.J. Taylor was really Jeff Webber's son Steven Lars. Peter Taylor died of a heart attack when he heard. Diana Taylor realized that she could lose her little boy forever... unless she married Jeff.

In 1980, while Heather was still in the Sanitarium, Jeff fell in love with Audrey's niece Annie Logan and the duo hoped to wed. At the same time, Diana wanted to marry Jeff so that she could keep her son. Also, Heather faked catatonia and escaped from the sanitarium. She saw Jeff holding Annie in his arms. She went back to the Sanitarium but was soon released.

In 1981, Annie and Jeff had broken up and Jeff started a hot affair with Diana. Heather, who had again faked being insane, escaped from the sanitarium again and saw the two making love. Diana, who was still hoping for a future with Jeff, finally revealed to him that P.J. was his son. Jeff was angry and stormed out of the apartment. At wits end, Diana pleaded with him to stay. Minutes later, Diana was dead. Heather found the body and wrote Anne's name in blood framing her for the murder. There was a clear-cut case against Annie Logan and Jeff decided that he needed to leave town. Jeff took little Steven Lars and left Port Charles, later asking Heather for a divorce because he found someone else. In 1997, Jeff and his wife traveled to Sarajevo to help in the war effort. They sent their eldest daughter Sarah to live with her 'grandmother' Audrey. Their youngest daughter Elizabeth was left with family friends, but she ran away after a few months and joined her sister in Port Charles. In 1998, Jeff wrote to Sarah and had her move to Sarajevo.

In 2016, it was revealed that Jeff had met Naomi Dreyfus years earlier, and the two had an affair that resulted in the birth of Hayden Barnes. In 2022, Elizabeth's son Jake revealed that Jeff, along with Carolyn, had reached out to him through online messaging and texts. In October 2022, it was revealed that Jeff had been stationed with Dr. Hamilton Finn in the Mariana Islands around the time of Finn's wife's death.