The 6 ft Striker has put pen-to-paper on a two-year deal and will re-unite with manager Jim Smith for a second time.
Twigg started his career at Derby County and had loan spells with Burton Albion and Bristol Rovers before making a permanent switch to Airdrie in August, 2005.
He can play on the left wing or up front and made over 50 appearances in the Scottish First division, scoring 17 goals in the process.
Oxford United chairman Nick Merry told BBC Radio Oxford: "He's got a good record and he's very versatile too.
"He can play wide or down the middle and he'll be a good asset to us."
Source: http://www.confguide.com/newsArticle.do?id=6756