A late touchdown helped the San Francisco 49ers come from behind to beat the Kansas City Chiefs.
The AFC West side, led by former 49ers quarterback Alex Smith, took the lead early on as Quintin Demps returned a kickoff for a 104-yard touchdown.
However, the 49ers' defense was able to sack Smith three times to prevent the Chiefs from increasing their lead, before a 14-yard touchdown from Chuck Jacobs ensured that the Super Bowl runners-up secured a 15-13 win.
Tom Brady got the New England Patriots off to a strong start in their win over the Tampa Bay Buccaneers.
The quarterback, who sustained a mild knee sprain in practice this week, found Danny Amendola for a first-quarter touchdown while completing 11 of his 12 passes for 107 yards.
Buccaneers quarterback Josh Freeman had a tough time, being sacked three times in the first quarter, but backup Mike Glennon was able to complete two touchdown passes to keep the game close.
Rookie quarterback EJ Manuel continued to impress as the Buffalo Bills claimed a 20-16 win over the Minnesota Vikings.
The first-round draft pick completed 10 of his 12 attempts for 92 yards and a touchdown, while Kevin Kolb, who is competing with Manuel to be the team's starter, managed 13 from 21 for 111 yards and an interception.
The Vikings, who rested league MVP Adrian Peterson, were strong in the fourth quarter, with Joe Banyard and Rodney Smith finding the end zone.
The New Orleans Saints survived an Oakland Raiders fightback to secure their second win of the pre-season.
The NFC South side led 23-7 at half time, with Mark Ingram and Kenny Stills both scoring touchdowns as quarterback Drew Brees completed 202 passing yards.
Denarius Moore got the Raiders off the mark just before the break, while defensive end Ryan Robinson returned a fumble for a touchdown in the third quarter.
The AFC West team reduced the Saints' lead to three points, but a late safety and field goal secured the win for Sean Payton's side.
Results in full: Minnesota Vikings 16-20 Buffalo Bills, San Francisco 49ers 15-13 Kansas City Chiefs, Tampa Bay Buccaneers 21-25 New England Patriots, Oakland Raiders 20-28 New Orleans Saints