Alfredsson reached the milestone at 3:31 of overtime to cap Ottawa's come-from-behind 4-3 win over the Calgary Flames on Friday night.
The Senators' longtime captain drove a slap shot from the left point past Leland Irving on a power play after Calgary was left short-handed when Rene Bourque was called for holding 2:20 into the extra period.
"To be able to do this at home and in overtime, when everybody's still in the building and being a big goal for us, it's almost too good to be true," said the 39-year-old Swedish right wing, who was "too mobbed" by his teammates to get a look at a replay on Scotiabank Place's new HD video scoreboard.
Alfredsson's 400th goal was his 1,050th point in his 1,088th regular-season game — all team records.
"We're really happy for Alf," said centre Jason Spezza, who was on the ice for the milestone. "To score his 400th goal is a huge milestone, and to do it in overtime, in a dramatic game — we were down three goals, at home, with his family here, I think we were all pretty happy for him and just excited as teammates."
Erik Karlsson, who assisted on Alfredsson's milestone goal, tied it at 3-3 with an unassisted effort 4:28 into the third as Ottawa battled back from an early 3-0 deficit.
Karlsson picked up his own rebound and circled behind the net with a delayed penalty signalled against Calgary. The smooth-skating defenceman came out the other side to score his fifth goal.
Nick Foligno and Zack Smith scored in the second period for the Senators.
Bourque, Curtis Glencross and Chris Butler scored first-period goals to give the Flames a 3-0 lead.
CAPITALS 3, SABRES 1
WASHINGTON (AP) — Alex Ovechkin scored early and late, Tomas Vokoun made 25 saves, and Washington beat Buffalo.
One of Ovechkin's two goals was actually a pass attempt that got deflected into the net, but the Capitals captain has five goals in seven games, a further sign that he is emerging from the spotty play that has run parallel to Washington's slow start. The former two-time NHL MVP has 14 goals on the season.
Nicklas Backstrom also scored his 13th of the season — his 100th career NHL goal — for the Capitals. Alexander Semin had a pair of assists for his second multipoint game in a row.
Jochen Hecht scored for the Sabres. Ryan Miller made 18 saves.
RANGERS 4, PANTHERS 1
SUNRISE, Fla. (AP) — Carl Hagelin had a goal and an assist, Henrik Lundqvist stopped 27 shots, and New York earned a victory against Florida.
Brad Richards, Michael Del Zotto, and Brandon Dubinsky also scored for the Rangers, who have won six of seven and will play the Philadelphia Flyers in the Winter Classic on Monday in Citizens Bank Park.
Ryan McDonagh had two assists for New York, which leads the Eastern Conference with 50 points.
Matt Bradley scored for the Panthers.
BLACKHAWKS 3, RED WINGS 2
CHICAGO (AP) — Brent Seabrook scored a goal to break a tie early in the third period, and Chicago defeated Detroit.
Seabrook scored the game-winner 1:52 into the third when he fired from the blue line and overpowered Detroit goalie Jimmy Howard with a rising shot that sailed over his glove.
Marian Hossa scored and Jonathan Toews connected on a penalty shot for Chicago, which improved to 10-2-1 in its past 13 before a season-high crowd of 22,166 at the United Center.
Justin Abdelkader and Todd Bertuzzi had goals for the Red Wings.
The win gave Chicago 52 points. The Blackhawks, in first place in the Central Division, opened a five-point lead on second-place Detroit.
PREDATORS 2, BLUES 1, SO
ST. LOUIS (AP) — Martin Erat scored in the fifth round of the shootout to give Nashville a victory over St. Louis.
Erat sent a shot high over the glove hand of Jaroslav Halak and Pekka Rinne kept the Blues scoreless on all five attempts to win for the second game in a row in a shootout.
Matt Halischuk scored for the Predators. Rinne stopped 35 shots.
The Blues got a goal from T.J. Oshie. Halak stopped 33 shots.