The most anticipated Buffalo Bills season of the past decade (or perhaps the past two decades?) will begin with two of the Bills' toughest games of the year, against the New England Patriots and Indianapolis Colts. It will also include the franchise's first stretch of five road games in six weeks since 1991. If Rex Ryan's bunch can keep it steady through those two trouble spots, they stand a chance of making the playoffs.

Week 1: Sunday, Sept. 13, Indianapolis, 1 p.m.

Andrew Luck's first career trip to Ralph Wilson Stadium might not go well, especially against a Bills defense that gave Aaron Rodgers his worst-ever game last season. But can the Bills' offense -- with so many new pieces and a quarterback potentially making his first start in a Bills uniform -- jell this quickly? It'll be tough. Colts 24, Bills 21. Record 0-1.

Week 2: Sunday, Sept. 20, New England, 1 p.m.

The Bills host the Patriots in an early-season game for fifth consecutive year, and each time the Bills have either kept it close or won. Throw in Tom Brady's career struggles against Ryan-coached defenses and this is a winnable game. Bills 28, Patriots 24. Record 1-1.

Week 3: Sunday, Sept. 27, at Miami, 4:25 p.m.

The Bills don't catch any favors with this early-season trip to South Florida, where the heat and humidity give road teams trouble in September. Kyle Orton won't be the quarterback again but the results could be similar to last season's flop on Thursday night, especially with a Bills offensive line dealing with a Dolphins defense that has added Ndamukong Suh. Dolphins 27, Bills 17. Record 1-2.

Week 4: Sunday, Oct. 4, NY Giants, 1 p.m.

This is where the Bills' schedule starts to ease up. The Giants are a shell of the team that won a Super Bowl four seasons ago. I just don't see Eli Manning posing a threat to this Bills defense. Bills 26, Giants 13. Record 2-2.

Week 5: Sunday, Oct. 11, at Tennessee, 1 p.m.

Unless the Titans trade for Philip Rivers and miraculously pull it together, this game should be the easiest on the Bills' schedule. The Titans are a mess. If the Bills lose this one, sound the alarm. Bills 35, Titans 20. Record 3-2.

Week 6: Sunday, Oct. 18, Cincinnati, 1 p.m.

The Bengals are the Bills' biggest speed bump in an otherwise soft October slate. I don't see Andy Dalton giving the Buffalo defense any problems, especially on its home turf, but I would have concerns about the Bills' yet-to-be-named quarterback against that stingy Bengals defense. This is a tight one that could go to overtime like these teams' 2013 meeting at Ralph Wilson Stadium. Bengals 24, Bills 21. Record 3-3.

Week 7: Sunday, Oct. 25, Jacksonville (in London), 9:30 a.m.

This game will be played in a different environment (actually, a different continent), making it somewhat harder to predict. I think the Jaguars have the potential to be better this season but I just don't see Blake Bortles tearing up this Bills defense on the Wembley Stadium turf. Bills 31, Jaguars 17. Record 4-3.

Week 9: Sunday, Nov. 8, Miami, 1 p.m.

Will the Dolphins show up to play at Ralph Wilson Stadium this season? They effectively haven't the past two seasons, with the Bills blowing them out each time. I don't see that changing. Bills 28, Dolphins 10. Record 5-3.

Week 10: Thursday, Nov. 12, at NY Jets, 8:25 p.m.

This is where the Bills' schedule starts to tighten up. This is a winnable game for the Bills -- they went into MetLife Stadium last season and blew the Jets out -- but I have a feeling it won't be so easy this time around. The Bills will have a short week and the atmosphere, with Ryan returning to New Jersey, will be charged. I'll give the slight edge to the improved Jets in prime time. Jets 23, Bills 19. Record 5-4.

Week 11: Monday, Nov. 23, at New England, 8:30 p.m.

The Bills' first Monday Night Football tilt since 2009 will take place in Gillette Stadium, which has been a house of horrors for Buffalo. We know Ryan will have this game circled on his calendar, and if he can pull it out, it will be a big statement for his team in the AFC East. But it'll be the Bills' biggest hurdle this season. Patriots 34, Bills 24. Record 5-5.

Week 12: Sunday, Nov. 29, at Kansas City, 1 p.m.

Mental toughness will be no more important than this weekend, when the Bills -- on short rest -- will play their third consecutive road game. In what could be Matt Cassel's return to Kansas City, the Bills will have to battle late-season travel fatigue and the Arrowhead Stadium crowd. That's not an ideal combination. Chiefs 20, Bills 14. Record 5-6.

Week 13: Sunday, Dec. 6, Houston, 1 p.m.

With the season on the ropes, the Bills will have a chance to catch their breath and avenge last season's loss to Houston. I can see this being a game where Ryan rallies his troops after a tough road stretch and gets his team back on track in a big way. Bills 38, Texans 17. Record 6-6.

Week 14: Sunday, Dec. 13, at Philadelphia, 1 p.m.

LeSean McCoy's return to Philadelphia and a chess match between Ryan, the defensive wizard, and Chip Kelly, the offensive guru, adds some late-season intrigue, so this one has the potential to get flexed to a late-afternoon or night game. Like the Bengals home game in October, I see this going either way. The playoffs could be on the line. Eagles 24, Bills 21. Record 6-7.

Week 15: Sunday, Dec. 20, at Washington, 1 p.m.

With their backs against the wall, the Bills make another trip to an NFC East opponent and start to make their final push to the playoffs. Like the Titans, the Redskins are a team without much direction. The Bills need to take advantage of this one. Bills 27, Redskins 14. Record 7-7.

Week 16: Sunday, Dec. 27, Dallas, 1 p.m.

This late in the season, you never know what version of the Cowboys you'll get. Will they be a fragile team on the verge of collapse or serious contenders in the NFC? Either way, I can see the Bills and their fans coming together to keep Buffalo's playoff hopes alive. Bills 33, Cowboys 21. Record 8-7.

Week 17: Sunday, Jan. 3, NY Jets, 1 p.m.

It's the final week of the season and the Bills, entering with a record that could put them on the playoff bubble, will be watching the scoreboard closely. The Jets, meanwhile, could be out of the picture. Advantage Buffalo. Bills 24, Jets 13. Record 9-7.