Two first half strikes from Stuart Gray (10 pen & 34) gave Brian Talbot's men a great start and a late effort from Paul Hall (83) rounded off the win.
Southend had a torrid day, summed up by striker Graeme Jones who saw his late penalty well saved by Bill Turley.
Rushden went back to the summit, thanks to Hartlepool's failure to win at Swansea.
Chris Turner's outfit took the lead after just 14 minutes through Mark Tinkler, but player-boss Nick Cusack (28) and Jamie Wood (pen 43) gave the home side the advantage.
The Teessiders struck back, though, just before the interval with a Gordon Watson goal, which gave them a share of the spoils.
Cambridge failed to keep up the pace at the top of the table, a Hull City recorded their first win of the season at The Abbey Stadium.
The Tigers left it late to go into the lead, but did it in style with two goals in three minutes with goals from Justin Whittle (71) and Shaun Smith (74).
Dave Kitson pulled one back in the final minutes for the home side, but it was too little too late for John Taylor's men.
A good crowd at Sincil Bank saw Lincoln City beat Scunthorpe 1-0 in the Lincolnshire derby.
Ben Futcher's header just before half time was enough to separate the two sides - the three points sees the Red Imps move into the top three.
Shrewsbury came from behind at Gay Meadow to beat Leyton Orient 2-1.
Matt Lockwood had put the Londoners in front after just five minutes, but Luke Rodgers levelled matters just after the interval.
Lee Thorpe was then sent off for Orient, which disrupted their rhythm and Town grabbed the winner through Nigel Jemson with 14 minutes remaining.
Oxford produced a remarkable comeback at The Kassam Stadium, as two late strikes earned them a 2-2 draw against in-form Torquay.
Goals from David Graham (48) and Tony Bedeau (79) had looked to have given The Gulls their third win in three games.
However, late strikes from substitute Manny Omoyinmi and Paul Powell gave Oxford a point.
Bournemouth earned a good three points at St James' Park with a 2-1 win over Exeter.
Andy Roscoe had given the home side the lead after just seven minutes, but goals from Alan Connell (36) and Wade Elliott (41 pen) put The Cherries in front.
Gareth O'Connor wrapped up the game with 17 minutes left for Bournemouth. Just a minute before Exeter's Brazilian Santos Gaia was sent off again for The Grecians.
Newly promoted Boston are still bottom of the table, but they will be happy with their 0-0 draw with Kidderminster at Aggborough.
Click below for match summaries:
Cambridge United 1-2 Hull City
Exeter City 1-3 Bournemouth
Kidderminster Harriers 0-0 Boston United
Lincoln City 1-0 Scunthorpe United
Oxford United 2-2 Torquay United
Rushden & Diamonds 3-0 Southend United
Shrewsbury Town 2-1 Leyton Orient
Swansea City 2-2 Hartlepool United
