Jed Wallace opened the scoring in the 20th minute, David Connolly made it two six minutes later and, after Andy Wright had been sent off, Patrick Agyemang wrapped up a 3-0 victory six minutes before the break.
Southend have made their best start to a season in 23 years and share top billing with Oxford.
It was a horrible day for Northampton, who saw former Southend striker Roy O'Donovan miss a penalty in the eighth minute and then had Chris Hackett sent off with more than an hour left.
Oxford lead the table on goal difference after a 3-1 victory over Torquay.
Striker James Constable was instrumental in Chris Wilder's side claiming their third league win in a row, scoring a superb 62nd-minute goal and laying on the third for fellow substitute Asa Hall (78).
Dean Smalley opened the scoring in the 49th minute, with Torquay's effort coming from Jordan Chapell (70).
Chesterfield lost their 100 per cent record after being held to a 2-2 draw at Rochdale.
Marc Richards (19) opened the scoring for the visitors but Rochdale levelled 10 minutes later at the second attempt.
George Donnelly missed a penalty only for Dale to be awarded a second spot-kick moments later, which Andrew Tutte converted.
The hosts went ahead six minutes after the break through Scott Hogan but Gary Roberts restored parity with 25 minutes left.
Andy Sandell's 42nd-minute penalty was the only goal of the game as Newport continued their fine start to life in League Two with a 1-0 win over cross-border rivals Bristol Rovers.
The sides had not faced each other in a competitive fixture since Rovers claimed the spoils 25 years ago.
John O'Flynn's first-half brace ensured Exeter maintained their unbeaten start to the season in with a 2-0 win over AFC Wimbledon.
Fleetwood and Burton have both made good starts and they provided plenty of entertainment as Albion ran out 3-2 winners.
The first half eventually proved decisive, with Rene Howe, Adam McGurk and Chris Hussey all netting for Burton.
They were made to sweat, though, as Jeff Hughes (65) and Jamille Matt (72) pulled goals back, but Fleetwood could not find an equaliser.
Bury bagged their first League Two win of the season with a 3-0 defeat of 10-man Accrington.
Loan pair Anton Forrester and Jordan Sinnott came both scored in the first half, either side of a straight red card for Stanley striker Danny Webber.
Substitute Marlon Jackson then netted late on to leave the visitors waiting for their first league win.
Plymouth got their season up and running with an impressive 3-1 victory at Cheltenham.
Without a point or a goal going into the match at Whaddon Road, Arygle surprised their hosts by racing into a 3-0 half-time lead with goals from Marvin Morgan, Conor Hourihane and Romuald Boco.
Matt Richards netted a free-kick for Cheltenham in the 72nd minute.
An injury-time equaliser from Luke Howell salvaged Dagenham a point in a 1-1 draw at Scunthorpe.
All the drama happened late on, with Chris Iwelumo missing a 70th-minute penalty for Scunthorpe, who did then take the lead through David Mirfin two minutes from time only for Howell to strike.
Substitute Ollie Palmer scored Mansfield's first goal since their return to the Football League 12 minutes from time to earn a 1-0 win over Wycombe while Hartlepool earned their first point in a goalless draw with York.