The Bills also signed veteran linebacker David Hawthorne.
Spikes reflected on his return to the Bills in a tweet Sunday.
Spikes, 28, last played in the NFL for the Bills in 2014. He signed with the New England Patriots last year but was released in June 2015 as police investigated his role in a hit-and-run crash in Massachusetts. Spikes later pleaded guilty to multiple motor vehicle charges and received probation. The NFL suspended Spikes for the first four games of the 2015 regular season, which he spent out of football.
Hawthorne, 31, played the past four seasons for the New Orleans Saints. Bills assistant head coach/defense Rob Ryan coached Hawthorne from 2013 until the Saints fired him as defensive coordinator during the 2015 season.
The additions of Spikes and Hawthorne come after Ragland, the Bills' second-round pick in April, injured his left knee in Friday's practice. Coach Rex Ryan initially said Ragland avoided ligament damage to his knee, but he struck a less optimistic tone Saturday when speaking about the injury.
Initial MRI on Ragland's knee revealed what appears to be a partial ACL tear, but the team is confident it is not fully torn, a team source told ESPN NFL Insider Adam Schefter. The team is scheduled to get a second opinion of Ragland's MRI on Monday, and that will determine how much time the rookie second-round pick will miss. The Bills' first-round pick Shaq Lawson is out after undergoing shoulder surgery.
"I'm not real sure," Ryan said. "I guess I was just so hopeful there's not going to be ligament things. My understanding is that as you get going, your leg is so tight, they'll fight it. You don't really get a true look of that. So as we mentioned, we got to wait for that swelling to go down.
"I know every Bills fan out there is hoping for the best, and that's certainly what we're doing, but there is concern."
After spending his first four seasons with the Patriots, Spikes signed with the Bills in 2014 and started 10 games that season. Limited to mostly an early-down run-stopping role, Spikes tallied 54 tackles, one sack, one forced fumble and three passes defensed for Buffalo while serving as a team captain.
Information from ESPN's Adam Schefter was used in this report.