Sean Donely arrived in Port Charles after his good friend and occasional adversary Robert Scorpio requested his assistance. Sean and Robert had worked together in the World Security Bureau (WSB). Robert and his friend Luke Spencer had run into trouble as they searched for the Aztec treasure. Although Sean had offered his help, he secretly had his sights set on the treasure as well and looked forward to outwitting Robert. Despite the competition between them for the treasure, Sean and Robert remained close, and Sean remained in Port Charles to help Robert protect his family from the dangers of Mr. Wu. In return, Robert made Sean his daughter's godfather.

Sean spent time with Robert and his wife Anna but also made time for married woman Monica Quartermaine. Sean and Monica engaged in an affair, but he became interested in Tiffany Hill. His ability to pursue Tiffany was limited after Monica's husband, Alan, was believed murdered. Sean was the main suspect. Eventually Alan was revealed to be alive, and Sean was able to pursue a relationship with Tiffany.

Tiffany and Sean grew closer and married in 1988. Tiffany took a position working at a television station while Sean tried to live a quiet life away from the adventures of his past. However, Sean's previous involvements with criminals such as Cesar Faison and the Cartel often forced him to team up with Anna and Robert, as well as Frisco Jones and his wife Felicia. At one point, Faison blackmailed Sean into compliance by administering poison to Tiffany. She was temporarily comatose but later made a full recovery.

Robert and Anna left town to deal with Faison, and Sean took over the role of police commissioner in their absence. Meanwhile, Tiffany made plans to adopt her deceased sister's son, Lucas, but Sean did not support her decision. Bobbie and Tony Jones had adopted Lucas, and her sister's will had also given custody to the Jones family. The difference of opinion placed their marriage under great strain, and Sean found comfort in the arms of lawyer Jessica Holmes.

The desire Tiffany had to raise her nephew dissipated after she discovered she was pregnant. Jessica realized that Sean and Tiffany were growing closer and announced that she was pregnant as well. Tiffany suffered a miscarriage, and afterward, Jessica admitted that she had lied about the pregnancy. However, Jessica really was pregnant but was murdered soon after. Sean believed that Tiffany had committed the murder and confessed to the crime in order to protect his wife. The real murderer, Ryan Chamberlain, was later revealed.

Sean's marriage to Tiffany survived his affair, and they remained committed to one another. She offered her full support to Sean after he was accidentally shot and injured by Luke during a shootout with mobster Frank Smith. The best medical treatment was located in Boston, and Sean and Tiffany relocated there. Just before they left, Tiffany learned that she was pregnant. It was later revealed that they had a daughter and named her Anna after their good friend.

Several years later, Luke, along with Holly Sutton, tracked Sean down in Ireland after they realized he was somehow connected to Jerry Jacks and the cure for the Polonium-210 poisoning, which Luke sought. Sean confessed that he had been poisoned with the radioactive substance just like Luke and Jerry. Sean had known of Jerry's plan to poison the Port Charles water supply in exchange for the money to pay for a cure. He had picked up the money for Jerry, and his payment would be the cure. However, instead of the remedy, Sean only received a temporary medication, which lessened the symptoms. Sean offered to partner with Luke in his search for Jerry and the cure. With help from Tracy Quartermaine, Luke acquired the antidote and shared it with Sean.