"I have been waiting 174 days to say this," Roberts said. "Good morning, America."
Roberts had been on medical leave from "GMA" since the end of August, when she left to have treatment a rare blood and bone marrow disorder called MDS.
"This feels right," Sam Champion said with a smile after Robin's introduction.
Roberts' comeback came five months to the day since she underwent a bone marrow transplant from her sister Sally.
At the studio, ABC boss Anne Sweeney, news division President Ben Sherwood and Katie Couric all stood in the wings watching. When Roberts thanked her nurses on the air, all of the show producers in the control room a floor away stood and applauded. Sherwood delivered a champagne toast on the set after the show went off the air at 9 a.m.
"Can I go home now?" Roberts said, before delivering a tearful thank you to her colleagues.
Bottles of hand sanitizers were kept nearby for people who come into regular contact with Roberts, who must try to avoid contact with others as her immune system builds back up. The plan is for Roberts to work two or three days a week initially and her health will be closely monitored, said Tom Cibrowski, the show's senior executive producer.
Roberts said after the show that she wasn't tired and was working on adrenaline. But the bright studio lights affected her eyesight. She said she started having trouble seeing the teleprompters midway through the show.
She was given the okay to return to the show last month, after doctors told her that her blood count was improving.
Robin tweeted Tuesday night, saying: "Thank you! Blessings to each and everyone one for loving me through it. May it be returned 10 fold. G'Night..see you in the morning. XO".
In addition to returning to the show, Roberts will share her personal journey battling MDS on a special edition of 20/20 Friday at 10 p.m. ET.
LINK: LORI STOKES SITS DOWN WITH ROBIN AFTER SHOW
