The 10-year veteran finished 7-5 in 12 starts with the Bills this season. He went 287-of-447 for 3,018 yards, with 18 touchdowns and 10 interceptions.
Orton told the Bills on Monday: "I just have been going at it for 10 years and it’s just a family decision and I’ve decided to get home and be a dad and call it a day.
"I think I've been away from my parents since going to college, so 14 years.
"Anytime you have a chance to end on a good note and go home and spend time with family that's really important to me and my wife and we're just excited to move on.
"It's not a decision based on anything football-wise, just a family decision and one I'm going to stick to."
Orton spent the previous two seasons with the Dallas Cowboys but was waived in July and signed a two-year deal with the Bills six weeks later.
He replaced EJ Manuel as the starting quarterback heading into week five and kept the job for the rest of the season.
Orton, 32, previously played for the Kansas City Chiefs, the Denver Broncos and the Bears after Chicago picked the former Purdue standout in the fourth round of the 2005 draft.