Changes on the offensive line may have contributed: veteran tackle Stan Brock retired during the offseason, and center Courtney Hall suffered a career-ending injury mid-season.
Touchdowns by Tony Martin and Leonard Russell, plus five field goals by John Carney saw the Chargers to an easy win on opening day.
However, the Bengals came back into it before halftime when Carl Pickens scored; Humphries then threw an interception with San Diego poised to respond.
Firstly, Darrien Gordon's 64-yard punt return set up a short field goal; on the Bengals' next play from scrimmage Kurt Gouveia intercepted Jeff Blake, and Russell soon punched it in from the one.
Edgar Bennett scored on the Packers' opening drive, and Brett Favre followed up with 3 touchdown passes as Green Bay built a 28–3 lead through three-quarters.
The Chargers broke the game open late in the 1st quarter when Stan Humphries threw touchdown on three consecutive pass attempts.
Kurt Gouveia intercepted Jeff Hostetler's next pass, leading to an even shorter drive, with Martin scoring the Chargers' second touchdown.
Following a further exchange of field goals, Seau intercepted Steve Bono for the second time, and Carney kicked the winner from 33 yards out with 3:17 to play.
Given a bonus chance, Bono led his team into field goal range, but Chris Mims blocked the game-tying attempt.
John Elway responded immediately, leading his team 80 yards in just five plays, the last 20 coming on a 20-yard strike to Shannon Sharpe shortly before halftime.
San Diego tried to respond, but Humphries threw incomplete on 4th and 7 at the Broncos' 38, and Elway soon put the game away with his fourth touchdown pass, this time to Ed McCaffrey.
With his side down 7–0 in the 1st quarter, Humphries was hit by Chester McGlockton at the end of a 5-yard scramble and dislocated his left shoulder; backup Sean Salisbury came in and finished the drive with an 11-yard touchdown pass to Martin.
Colts' QB Jim Harbaugh was intercepted by four different players in the first half — he had thrown only two all season coming in — and the Chargers converted the errors into a Charlie Jones touchdown reception and a pair of field goals.
These were the first in a sequence of eight fields, four by each team, culminating in a Colts 20-yarder that made it 19–12; Indianapolis almost had a touchdown before that last kick, but punter Darren Bennett brought down Ray Buchanan at the nine after an 82-yard return.
Indianapolis were driving at the start of the 4th quarter, but Junior Seau sacked Harbaugh, causing a fumble which Chris Mims recovered.
Stan Humphries had a successful return to the starting lineup, and San Diego overcame another slew of penalties to win their second straight.
The Lions led 14–10 on the stroke of halftime, but Humphries lofted a high pass into the end zone as the clock ran out, which eluded several Detroit defenders and nestled in the arms of Andre Coleman for a 46-yard touchdown.
It was the second time Humphries had completed a Hail Mary pass on Monday Night Football, having done the same against Miami three seasons earlier.
Carney had the chance to make the game almost safe with 5 minutes to play, but missed a 49 yarder, and Don Majkowski led Detroit the other way for a touchdown.
San Diego suffered a shock defeat against the Buccaneers, who were 2-8 coming in, had lost ten consecutive road games, and had zero wins against the Chargers from six previous attempts.
After Tampa Bay missed a short field goal, the Chargers recovered a muffed punt and scored via Russell a play later.
The Buccaneers pulled it back to 14–10 over their next two drives, then began to miss numerous chances: Trent Dilfer was stuffed attempting a QB sneak on 4th and 1 from the San Diego 30; Alvin Harper dropped a pass in the end zone, forcing his team to settle for a field goal as the first half ended; following a Humphries interception, Dilfer was sacked by Chris Mims on 1st and 10 from the Charger 17, and Reuben Davis recovered; following a San Diego field goal, the Buccaneers executed a fake punt and reached 1st and 5 from the Charger 20, but Dilfer threw it straight to Rodney Harrison in the end zone.
After Martin had opened the scoring, Kansas City reached a 3rd and 5 at the Charger 20, but Harrison intercepted Steve Bono, and San Diego drove 97 yards the other way to a Russell touchdown.
The Patriots scored touchdowns on their first two drives, before Stan Humphries found Tony Martin from 46 yards out to halve the deficit.
Patriots' QB Drew Bledsoe threw four touchdowns, the last of these to former Charger Shawn Jefferson, and Humphries was knocked out of the game in the 3rd quarter with a concussion.
The Chargers offense, which once again had Salisbury in as starting QB, had mustered few threats to that point, but managed to get inside the Pittsburgh 10 before settling for a field goal.
A 50-yard catch by Andre Coleman helped San Diego reach 3rd and 2 at the five yard line on their next possession, but Russell fumbled the chance away.
John Elway started the game, and had his side up 10–0 before losing a fumble which Seau recovered, setting up a Humphries-to-Jones touchdown pass.
With Terrell Davis soon joining his quarterback on the sidelines, the Denver offense was led by backups, and could generate no further points; Rodney Harrison foiled their best chance with an end zone interception.
The result meant that Bobby Ross left San Diego as the first Charger head coach to post no losing records during his tenure.