Holmes, 27, has signed a two-and-a-half year contract after scoring once in a four-game loan spell with the Cobblers.
Left-back Newey, 32, had a loan spell with Northampton last November and was released by Oxford on Monday.
"I thought he was outstanding when he came here," manager Chris Wilder told BBC Radio Northampton.
"He was superb for me at Oxford, we had a great defensive record there and he was a part of that."
"Tom's a good player, it was a great opportunity to get him in and I'm sure he'll have a decent career here with us."
Newey joined the U's in July 2013, when Wilder was in charge, and made 62 appearances for the club.
The former Grimsby and Rotherham defender had his loan spell at Northampton cut short by an ankle injury after only three appearances.
Northampton Town have signed Portsmouth midfielder Ricky Holmes on a free transfer and agreed a deal with former Oxford United defender Tom Newey.